<?xml version="1.0" encoding="UTF-8"?>

<!--XBRL Document Created with Wdesk from Workiva-->
<!--Copyright 2022 Workiva-->
<!--r:0a623d8d-bd1b-4372-9870-f554b882a16f,g:6079c96a-98e5-4d92-b257-ad443a270486-->
<link:linkbase xmlns:link="http://www.xbrl.org/2003/linkbase" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xmlns:xbrldt="http://xbrl.org/2005/xbrldt" xsi:schemaLocation="http://www.xbrl.org/2003/linkbase http://www.xbrl.org/2003/xbrl-linkbase-2003-12-31.xsd">
  <link:arcroleRef arcroleURI="http://xbrl.org/int/dim/arcrole/all" xlink:type="simple" xlink:href="http://www.xbrl.org/2005/xbrldt-2005.xsd#all"/>
  <link:arcroleRef arcroleURI="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:type="simple" xlink:href="http://www.xbrl.org/2005/xbrldt-2005.xsd#hypercube-dimension"/>
  <link:arcroleRef arcroleURI="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:type="simple" xlink:href="http://www.xbrl.org/2005/xbrldt-2005.xsd#dimension-default"/>
  <link:arcroleRef arcroleURI="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:type="simple" xlink:href="http://www.xbrl.org/2005/xbrldt-2005.xsd#dimension-domain"/>
  <link:arcroleRef arcroleURI="http://xbrl.org/int/dim/arcrole/domain-member" xlink:type="simple" xlink:href="http://www.xbrl.org/2005/xbrldt-2005.xsd#domain-member"/>
  <link:roleRef roleURI="http://www.agnc.com/role/DocumentandEntityInformation" xlink:type="simple" xlink:href="agnc-20220331.xsd#DocumentandEntityInformation"/>
  <link:definitionLink xlink:role="http://www.agnc.com/role/DocumentandEntityInformation" xlink:type="extended" id="i9ba3f7f889d4490bbb67f67955e9b0fb_DocumentandEntityInformation">
    <link:loc xlink:type="locator" xlink:label="loc_dei_EntityInformationLineItems_6d9351df-3a17-4de5-9914-a41be8677d6b" xlink:href="https://xbrl.sec.gov/dei/2021q4/dei-2021q4.xsd#dei_EntityInformationLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_Security12bTitle_0b3fb35d-f2aa-4895-b0a6-4847e6f5f2f9" xlink:href="https://xbrl.sec.gov/dei/2021q4/dei-2021q4.xsd#dei_Security12bTitle"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_dei_EntityInformationLineItems_6d9351df-3a17-4de5-9914-a41be8677d6b" xlink:to="loc_dei_Security12bTitle_0b3fb35d-f2aa-4895-b0a6-4847e6f5f2f9" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_EntityIncorporationStateCountryCode_f474b049-50e7-49ae-8ac3-340f20d068f4" xlink:href="https://xbrl.sec.gov/dei/2021q4/dei-2021q4.xsd#dei_EntityIncorporationStateCountryCode"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_dei_EntityInformationLineItems_6d9351df-3a17-4de5-9914-a41be8677d6b" xlink:to="loc_dei_EntityIncorporationStateCountryCode_f474b049-50e7-49ae-8ac3-340f20d068f4" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_DocumentTransitionReport_ff032099-7333-4dd1-93c4-8985a2fda645" xlink:href="https://xbrl.sec.gov/dei/2021q4/dei-2021q4.xsd#dei_DocumentTransitionReport"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_dei_EntityInformationLineItems_6d9351df-3a17-4de5-9914-a41be8677d6b" xlink:to="loc_dei_DocumentTransitionReport_ff032099-7333-4dd1-93c4-8985a2fda645" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_DocumentQuarterlyReport_e88e2ffd-7f30-4ee6-a603-ef5acd98d122" xlink:href="https://xbrl.sec.gov/dei/2021q4/dei-2021q4.xsd#dei_DocumentQuarterlyReport"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_dei_EntityInformationLineItems_6d9351df-3a17-4de5-9914-a41be8677d6b" xlink:to="loc_dei_DocumentQuarterlyReport_e88e2ffd-7f30-4ee6-a603-ef5acd98d122" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_EntityTaxIdentificationNumber_181ad14b-6a9f-49ce-9fee-86c56b3b4d2d" xlink:href="https://xbrl.sec.gov/dei/2021q4/dei-2021q4.xsd#dei_EntityTaxIdentificationNumber"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_dei_EntityInformationLineItems_6d9351df-3a17-4de5-9914-a41be8677d6b" xlink:to="loc_dei_EntityTaxIdentificationNumber_181ad14b-6a9f-49ce-9fee-86c56b3b4d2d" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_DocumentType_5607bae8-c805-4374-a19b-18775f10e99d" xlink:href="https://xbrl.sec.gov/dei/2021q4/dei-2021q4.xsd#dei_DocumentType"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_dei_EntityInformationLineItems_6d9351df-3a17-4de5-9914-a41be8677d6b" xlink:to="loc_dei_DocumentType_5607bae8-c805-4374-a19b-18775f10e99d" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_AmendmentFlag_f327f157-5e06-4169-9982-003cefd6c656" xlink:href="https://xbrl.sec.gov/dei/2021q4/dei-2021q4.xsd#dei_AmendmentFlag"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_dei_EntityInformationLineItems_6d9351df-3a17-4de5-9914-a41be8677d6b" xlink:to="loc_dei_AmendmentFlag_f327f157-5e06-4169-9982-003cefd6c656" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_DocumentPeriodEndDate_7a2c59b0-e115-4a63-802d-f4ad0c3b19ed" xlink:href="https://xbrl.sec.gov/dei/2021q4/dei-2021q4.xsd#dei_DocumentPeriodEndDate"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_dei_EntityInformationLineItems_6d9351df-3a17-4de5-9914-a41be8677d6b" xlink:to="loc_dei_DocumentPeriodEndDate_7a2c59b0-e115-4a63-802d-f4ad0c3b19ed" xlink:type="arc" order="7"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_EntityFileNumber_793b211e-1a3a-4e40-93fc-7b7c608fb8fc" xlink:href="https://xbrl.sec.gov/dei/2021q4/dei-2021q4.xsd#dei_EntityFileNumber"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_dei_EntityInformationLineItems_6d9351df-3a17-4de5-9914-a41be8677d6b" xlink:to="loc_dei_EntityFileNumber_793b211e-1a3a-4e40-93fc-7b7c608fb8fc" xlink:type="arc" order="8"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_DocumentFiscalYearFocus_2c228d1e-527a-4af1-a07b-22251955c1d2" xlink:href="https://xbrl.sec.gov/dei/2021q4/dei-2021q4.xsd#dei_DocumentFiscalYearFocus"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_dei_EntityInformationLineItems_6d9351df-3a17-4de5-9914-a41be8677d6b" xlink:to="loc_dei_DocumentFiscalYearFocus_2c228d1e-527a-4af1-a07b-22251955c1d2" xlink:type="arc" order="9"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_DocumentFiscalPeriodFocus_97b7231b-a87e-4287-9aa7-2cf877fe1e25" xlink:href="https://xbrl.sec.gov/dei/2021q4/dei-2021q4.xsd#dei_DocumentFiscalPeriodFocus"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_dei_EntityInformationLineItems_6d9351df-3a17-4de5-9914-a41be8677d6b" xlink:to="loc_dei_DocumentFiscalPeriodFocus_97b7231b-a87e-4287-9aa7-2cf877fe1e25" xlink:type="arc" order="10"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_EntityRegistrantName_d77d481a-fb6d-4c63-9aa6-25d9305c1536" xlink:href="https://xbrl.sec.gov/dei/2021q4/dei-2021q4.xsd#dei_EntityRegistrantName"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_dei_EntityInformationLineItems_6d9351df-3a17-4de5-9914-a41be8677d6b" xlink:to="loc_dei_EntityRegistrantName_d77d481a-fb6d-4c63-9aa6-25d9305c1536" xlink:type="arc" order="11"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_EntityAddressAddressLine1_a229d09e-c6a2-41cf-8518-d0007be2c6d2" xlink:href="https://xbrl.sec.gov/dei/2021q4/dei-2021q4.xsd#dei_EntityAddressAddressLine1"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_dei_EntityInformationLineItems_6d9351df-3a17-4de5-9914-a41be8677d6b" xlink:to="loc_dei_EntityAddressAddressLine1_a229d09e-c6a2-41cf-8518-d0007be2c6d2" xlink:type="arc" order="12"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_EntityAddressCityOrTown_70984dd2-a6d0-45be-a96e-47f3eb6d5853" xlink:href="https://xbrl.sec.gov/dei/2021q4/dei-2021q4.xsd#dei_EntityAddressCityOrTown"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_dei_EntityInformationLineItems_6d9351df-3a17-4de5-9914-a41be8677d6b" xlink:to="loc_dei_EntityAddressCityOrTown_70984dd2-a6d0-45be-a96e-47f3eb6d5853" xlink:type="arc" order="13"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_EntityAddressStateOrProvince_5476ad34-4e9f-4e46-a323-140424676b27" xlink:href="https://xbrl.sec.gov/dei/2021q4/dei-2021q4.xsd#dei_EntityAddressStateOrProvince"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_dei_EntityInformationLineItems_6d9351df-3a17-4de5-9914-a41be8677d6b" xlink:to="loc_dei_EntityAddressStateOrProvince_5476ad34-4e9f-4e46-a323-140424676b27" xlink:type="arc" order="14"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_EntityAddressPostalZipCode_26ffb7f6-2d70-4417-b7e1-c55b85e45b44" xlink:href="https://xbrl.sec.gov/dei/2021q4/dei-2021q4.xsd#dei_EntityAddressPostalZipCode"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_dei_EntityInformationLineItems_6d9351df-3a17-4de5-9914-a41be8677d6b" xlink:to="loc_dei_EntityAddressPostalZipCode_26ffb7f6-2d70-4417-b7e1-c55b85e45b44" xlink:type="arc" order="15"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_CityAreaCode_f050c1cb-c096-4c3d-91d3-3290a694d4fc" xlink:href="https://xbrl.sec.gov/dei/2021q4/dei-2021q4.xsd#dei_CityAreaCode"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_dei_EntityInformationLineItems_6d9351df-3a17-4de5-9914-a41be8677d6b" xlink:to="loc_dei_CityAreaCode_f050c1cb-c096-4c3d-91d3-3290a694d4fc" xlink:type="arc" order="16"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_LocalPhoneNumber_d69e3216-752f-4e04-a4e9-0ec622b3d507" xlink:href="https://xbrl.sec.gov/dei/2021q4/dei-2021q4.xsd#dei_LocalPhoneNumber"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_dei_EntityInformationLineItems_6d9351df-3a17-4de5-9914-a41be8677d6b" xlink:to="loc_dei_LocalPhoneNumber_d69e3216-752f-4e04-a4e9-0ec622b3d507" xlink:type="arc" order="17"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_EntityCentralIndexKey_28e95c25-fb20-4e9c-ba2d-fa1e581e1ce2" xlink:href="https://xbrl.sec.gov/dei/2021q4/dei-2021q4.xsd#dei_EntityCentralIndexKey"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_dei_EntityInformationLineItems_6d9351df-3a17-4de5-9914-a41be8677d6b" xlink:to="loc_dei_EntityCentralIndexKey_28e95c25-fb20-4e9c-ba2d-fa1e581e1ce2" xlink:type="arc" order="18"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_EntityFilerCategory_59ebaa9e-41b6-4e62-8d33-62bedea356b9" xlink:href="https://xbrl.sec.gov/dei/2021q4/dei-2021q4.xsd#dei_EntityFilerCategory"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_dei_EntityInformationLineItems_6d9351df-3a17-4de5-9914-a41be8677d6b" xlink:to="loc_dei_EntityFilerCategory_59ebaa9e-41b6-4e62-8d33-62bedea356b9" xlink:type="arc" order="19"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_EntitySmallBusiness_d089e834-194e-4b2c-83e9-143294ca5426" xlink:href="https://xbrl.sec.gov/dei/2021q4/dei-2021q4.xsd#dei_EntitySmallBusiness"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_dei_EntityInformationLineItems_6d9351df-3a17-4de5-9914-a41be8677d6b" xlink:to="loc_dei_EntitySmallBusiness_d089e834-194e-4b2c-83e9-143294ca5426" xlink:type="arc" order="20"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_EntityEmergingGrowthCompany_8ac33656-b7e2-4e25-8dd4-5709f78ea77a" xlink:href="https://xbrl.sec.gov/dei/2021q4/dei-2021q4.xsd#dei_EntityEmergingGrowthCompany"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_dei_EntityInformationLineItems_6d9351df-3a17-4de5-9914-a41be8677d6b" xlink:to="loc_dei_EntityEmergingGrowthCompany_8ac33656-b7e2-4e25-8dd4-5709f78ea77a" xlink:type="arc" order="21"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_CurrentFiscalYearEndDate_c4f8ac5e-d434-4a4d-bf91-dbd6dc934e84" xlink:href="https://xbrl.sec.gov/dei/2021q4/dei-2021q4.xsd#dei_CurrentFiscalYearEndDate"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_dei_EntityInformationLineItems_6d9351df-3a17-4de5-9914-a41be8677d6b" xlink:to="loc_dei_CurrentFiscalYearEndDate_c4f8ac5e-d434-4a4d-bf91-dbd6dc934e84" xlink:type="arc" order="22"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_EntityCommonStockSharesOutstanding_cc7573c1-c4fb-4c6f-8c1e-f73bcc5351ed" xlink:href="https://xbrl.sec.gov/dei/2021q4/dei-2021q4.xsd#dei_EntityCommonStockSharesOutstanding"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_dei_EntityInformationLineItems_6d9351df-3a17-4de5-9914-a41be8677d6b" xlink:to="loc_dei_EntityCommonStockSharesOutstanding_cc7573c1-c4fb-4c6f-8c1e-f73bcc5351ed" xlink:type="arc" order="23"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_TradingSymbol_c8939c75-dc16-4424-861f-68760b906dcb" xlink:href="https://xbrl.sec.gov/dei/2021q4/dei-2021q4.xsd#dei_TradingSymbol"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_dei_EntityInformationLineItems_6d9351df-3a17-4de5-9914-a41be8677d6b" xlink:to="loc_dei_TradingSymbol_c8939c75-dc16-4424-861f-68760b906dcb" xlink:type="arc" order="24"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_SecurityExchangeName_596d67fc-056f-49cb-ac33-593f18826942" xlink:href="https://xbrl.sec.gov/dei/2021q4/dei-2021q4.xsd#dei_SecurityExchangeName"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_dei_EntityInformationLineItems_6d9351df-3a17-4de5-9914-a41be8677d6b" xlink:to="loc_dei_SecurityExchangeName_596d67fc-056f-49cb-ac33-593f18826942" xlink:type="arc" order="25"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_EntityWellKnownSeasonedIssuer_6d5d7e33-21dc-4185-ae79-98d3571127f1" xlink:href="https://xbrl.sec.gov/dei/2021q4/dei-2021q4.xsd#dei_EntityWellKnownSeasonedIssuer"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_dei_EntityInformationLineItems_6d9351df-3a17-4de5-9914-a41be8677d6b" xlink:to="loc_dei_EntityWellKnownSeasonedIssuer_6d5d7e33-21dc-4185-ae79-98d3571127f1" xlink:type="arc" order="26"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_EntityVoluntaryFilers_505d5819-9e14-4cc4-931f-3b2f82b250cc" xlink:href="https://xbrl.sec.gov/dei/2021q4/dei-2021q4.xsd#dei_EntityVoluntaryFilers"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_dei_EntityInformationLineItems_6d9351df-3a17-4de5-9914-a41be8677d6b" xlink:to="loc_dei_EntityVoluntaryFilers_505d5819-9e14-4cc4-931f-3b2f82b250cc" xlink:type="arc" order="27"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_EntityCurrentReportingStatus_5ec668df-5b8b-4e32-9a2a-f1bfc8cdc2a4" xlink:href="https://xbrl.sec.gov/dei/2021q4/dei-2021q4.xsd#dei_EntityCurrentReportingStatus"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_dei_EntityInformationLineItems_6d9351df-3a17-4de5-9914-a41be8677d6b" xlink:to="loc_dei_EntityCurrentReportingStatus_5ec668df-5b8b-4e32-9a2a-f1bfc8cdc2a4" xlink:type="arc" order="28"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_EntityInteractiveDataCurrent_3283aae3-5eba-4de4-a290-cfcf72018904" xlink:href="https://xbrl.sec.gov/dei/2021q4/dei-2021q4.xsd#dei_EntityInteractiveDataCurrent"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_dei_EntityInformationLineItems_6d9351df-3a17-4de5-9914-a41be8677d6b" xlink:to="loc_dei_EntityInteractiveDataCurrent_3283aae3-5eba-4de4-a290-cfcf72018904" xlink:type="arc" order="29"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_EntityShellCompany_dcb48722-c300-42a7-99a0-0a1d143b9b6e" xlink:href="https://xbrl.sec.gov/dei/2021q4/dei-2021q4.xsd#dei_EntityShellCompany"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_dei_EntityInformationLineItems_6d9351df-3a17-4de5-9914-a41be8677d6b" xlink:to="loc_dei_EntityShellCompany_dcb48722-c300-42a7-99a0-0a1d143b9b6e" xlink:type="arc" order="30"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_IcfrAuditorAttestationFlag_099bc7be-deb8-4ed1-922f-04148e4b9dd0" xlink:href="https://xbrl.sec.gov/dei/2021q4/dei-2021q4.xsd#dei_IcfrAuditorAttestationFlag"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_dei_EntityInformationLineItems_6d9351df-3a17-4de5-9914-a41be8677d6b" xlink:to="loc_dei_IcfrAuditorAttestationFlag_099bc7be-deb8-4ed1-922f-04148e4b9dd0" xlink:type="arc" order="31"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_AuditorFirmId_44216b1d-906e-492e-b865-60d5bcc94702" xlink:href="https://xbrl.sec.gov/dei/2021q4/dei-2021q4.xsd#dei_AuditorFirmId"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_dei_EntityInformationLineItems_6d9351df-3a17-4de5-9914-a41be8677d6b" xlink:to="loc_dei_AuditorFirmId_44216b1d-906e-492e-b865-60d5bcc94702" xlink:type="arc" order="32"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_AuditorName_ecc90a45-cc7a-43e5-b528-4b3a3adca21e" xlink:href="https://xbrl.sec.gov/dei/2021q4/dei-2021q4.xsd#dei_AuditorName"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_dei_EntityInformationLineItems_6d9351df-3a17-4de5-9914-a41be8677d6b" xlink:to="loc_dei_AuditorName_ecc90a45-cc7a-43e5-b528-4b3a3adca21e" xlink:type="arc" order="33"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_AuditorLocation_f85aa6a6-a413-4010-ba94-3ddfb71dc925" xlink:href="https://xbrl.sec.gov/dei/2021q4/dei-2021q4.xsd#dei_AuditorLocation"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_dei_EntityInformationLineItems_6d9351df-3a17-4de5-9914-a41be8677d6b" xlink:to="loc_dei_AuditorLocation_f85aa6a6-a413-4010-ba94-3ddfb71dc925" xlink:type="arc" order="34"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_EntitiesTable_3e842225-db17-427e-9ba5-37d174e1f0bd" xlink:href="https://xbrl.sec.gov/dei/2021q4/dei-2021q4.xsd#dei_EntitiesTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_dei_EntityInformationLineItems_6d9351df-3a17-4de5-9914-a41be8677d6b" xlink:to="loc_dei_EntitiesTable_3e842225-db17-427e-9ba5-37d174e1f0bd" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StatementClassOfStockAxis_d1dd8985-5467-4fd9-91ee-80d7e8d1c7e7" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_StatementClassOfStockAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_dei_EntitiesTable_3e842225-db17-427e-9ba5-37d174e1f0bd" xlink:to="loc_us-gaap_StatementClassOfStockAxis_d1dd8985-5467-4fd9-91ee-80d7e8d1c7e7" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ClassOfStockDomain_d1dd8985-5467-4fd9-91ee-80d7e8d1c7e7_default" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ClassOfStockDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_StatementClassOfStockAxis_d1dd8985-5467-4fd9-91ee-80d7e8d1c7e7" xlink:to="loc_us-gaap_ClassOfStockDomain_d1dd8985-5467-4fd9-91ee-80d7e8d1c7e7_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ClassOfStockDomain_fc1f11ef-3fd3-4963-a5f1-6058342d7b9a" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ClassOfStockDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_StatementClassOfStockAxis_d1dd8985-5467-4fd9-91ee-80d7e8d1c7e7" xlink:to="loc_us-gaap_ClassOfStockDomain_fc1f11ef-3fd3-4963-a5f1-6058342d7b9a" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CommonStockMember_d4ab63d6-bb34-46bd-a237-fc2deb81f25e" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_CommonStockMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockDomain_fc1f11ef-3fd3-4963-a5f1-6058342d7b9a" xlink:to="loc_us-gaap_CommonStockMember_d4ab63d6-bb34-46bd-a237-fc2deb81f25e" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_Depositoryshareseachrepresentinga11000thinterestinashareof7.750SeriesBCumulativeRedeemablePreferredStockMember_c80e6354-fb88-433e-855c-73ce52f46213" xlink:href="agnc-20220331.xsd#agnc_Depositoryshareseachrepresentinga11000thinterestinashareof7.750SeriesBCumulativeRedeemablePreferredStockMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockDomain_fc1f11ef-3fd3-4963-a5f1-6058342d7b9a" xlink:to="loc_agnc_Depositoryshareseachrepresentinga11000thinterestinashareof7.750SeriesBCumulativeRedeemablePreferredStockMember_c80e6354-fb88-433e-855c-73ce52f46213" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_Depositoryshareseachrepresentinga11000thinterestinashareof7.000SeriesCFixedtoFloatingRateCumulativeRedeemablePreferredStockMember_000961de-7bb0-4883-b5a2-551d397b99d1" xlink:href="agnc-20220331.xsd#agnc_Depositoryshareseachrepresentinga11000thinterestinashareof7.000SeriesCFixedtoFloatingRateCumulativeRedeemablePreferredStockMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockDomain_fc1f11ef-3fd3-4963-a5f1-6058342d7b9a" xlink:to="loc_agnc_Depositoryshareseachrepresentinga11000thinterestinashareof7.000SeriesCFixedtoFloatingRateCumulativeRedeemablePreferredStockMember_000961de-7bb0-4883-b5a2-551d397b99d1" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_Depositoryshareseachrepresentinga11000thinterestinashareof6.875SeriesDFixedtoFloatingRateCumulativeRedeemablePreferredStockMember_fcc413c7-f01f-4613-a25c-532eda662b9c" xlink:href="agnc-20220331.xsd#agnc_Depositoryshareseachrepresentinga11000thinterestinashareof6.875SeriesDFixedtoFloatingRateCumulativeRedeemablePreferredStockMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockDomain_fc1f11ef-3fd3-4963-a5f1-6058342d7b9a" xlink:to="loc_agnc_Depositoryshareseachrepresentinga11000thinterestinashareof6.875SeriesDFixedtoFloatingRateCumulativeRedeemablePreferredStockMember_fcc413c7-f01f-4613-a25c-532eda662b9c" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_Depositoryshareseachrepresentinga11000thinterestinashareof6.500SeriesEFixedtoFloatingRateCumulativeRedeemablePreferredStockMember_90bb4998-8053-4aef-934c-e87737c3c47e" xlink:href="agnc-20220331.xsd#agnc_Depositoryshareseachrepresentinga11000thinterestinashareof6.500SeriesEFixedtoFloatingRateCumulativeRedeemablePreferredStockMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockDomain_fc1f11ef-3fd3-4963-a5f1-6058342d7b9a" xlink:to="loc_agnc_Depositoryshareseachrepresentinga11000thinterestinashareof6.500SeriesEFixedtoFloatingRateCumulativeRedeemablePreferredStockMember_90bb4998-8053-4aef-934c-e87737c3c47e" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_Depositaryshareseachrepresentinga11000thinterestinashareof6.125SeriesFFixedtoFloatingRateCumulativeRedeemablePreferredStockMember_c21ac3a3-f8d4-4706-9e04-61abffbe8452" xlink:href="agnc-20220331.xsd#agnc_Depositaryshareseachrepresentinga11000thinterestinashareof6.125SeriesFFixedtoFloatingRateCumulativeRedeemablePreferredStockMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockDomain_fc1f11ef-3fd3-4963-a5f1-6058342d7b9a" xlink:to="loc_agnc_Depositaryshareseachrepresentinga11000thinterestinashareof6.125SeriesFFixedtoFloatingRateCumulativeRedeemablePreferredStockMember_c21ac3a3-f8d4-4706-9e04-61abffbe8452" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_LegalEntityAxis_63ee68b6-b6fe-4ecf-837b-e0aa1fcf28b9" xlink:href="https://xbrl.sec.gov/dei/2021q4/dei-2021q4.xsd#dei_LegalEntityAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_dei_EntitiesTable_3e842225-db17-427e-9ba5-37d174e1f0bd" xlink:to="loc_dei_LegalEntityAxis_63ee68b6-b6fe-4ecf-837b-e0aa1fcf28b9" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_EntityDomain_63ee68b6-b6fe-4ecf-837b-e0aa1fcf28b9_default" xlink:href="https://xbrl.sec.gov/dei/2021q4/dei-2021q4.xsd#dei_EntityDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_dei_LegalEntityAxis_63ee68b6-b6fe-4ecf-837b-e0aa1fcf28b9" xlink:to="loc_dei_EntityDomain_63ee68b6-b6fe-4ecf-837b-e0aa1fcf28b9_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_EntityDomain_64127a7d-82b0-4c12-8e27-08f38aeb8375" xlink:href="https://xbrl.sec.gov/dei/2021q4/dei-2021q4.xsd#dei_EntityDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_dei_LegalEntityAxis_63ee68b6-b6fe-4ecf-837b-e0aa1fcf28b9" xlink:to="loc_dei_EntityDomain_64127a7d-82b0-4c12-8e27-08f38aeb8375" xlink:type="arc" order="1"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.agnc.com/role/ConsolidatedBalanceSheetsParenthetical" xlink:type="simple" xlink:href="agnc-20220331.xsd#ConsolidatedBalanceSheetsParenthetical"/>
  <link:definitionLink xlink:role="http://www.agnc.com/role/ConsolidatedBalanceSheetsParenthetical" xlink:type="extended" id="i7ef0a29ff4df47c08e697735d69a7624_ConsolidatedBalanceSheetsParenthetical">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FinancialInstrumentsOwnedAndPledgedAsCollateralLineItems_b5204d86-dcdf-477a-9dde-4f7bcb182771" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FinancialInstrumentsOwnedAndPledgedAsCollateralLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SecurityOwnedAndPledgedAsCollateralFairValue_85617ffc-2bdd-4794-b12f-8b6c34aafd14" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_SecurityOwnedAndPledgedAsCollateralFairValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FinancialInstrumentsOwnedAndPledgedAsCollateralLineItems_b5204d86-dcdf-477a-9dde-4f7bcb182771" xlink:to="loc_us-gaap_SecurityOwnedAndPledgedAsCollateralFairValue_85617ffc-2bdd-4794-b12f-8b6c34aafd14" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PledgedFinancialInstrumentsNotSeparatelyReportedSecuritiesPledged_99e3b6c4-b870-4c0e-9748-d9be6aee89f0" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_PledgedFinancialInstrumentsNotSeparatelyReportedSecuritiesPledged"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FinancialInstrumentsOwnedAndPledgedAsCollateralLineItems_b5204d86-dcdf-477a-9dde-4f7bcb182771" xlink:to="loc_us-gaap_PledgedFinancialInstrumentsNotSeparatelyReportedSecuritiesPledged_99e3b6c4-b870-4c0e-9748-d9be6aee89f0" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentFairValue_9cc7c206-4f73-49f8-9c56-96884677d02f" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DebtInstrumentFairValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FinancialInstrumentsOwnedAndPledgedAsCollateralLineItems_b5204d86-dcdf-477a-9dde-4f7bcb182771" xlink:to="loc_us-gaap_DebtInstrumentFairValue_9cc7c206-4f73-49f8-9c56-96884677d02f" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PreferredStockLiquidationPreferenceValue_77eb053c-8be4-4567-b1ad-cfe58fe7e273" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_PreferredStockLiquidationPreferenceValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FinancialInstrumentsOwnedAndPledgedAsCollateralLineItems_b5204d86-dcdf-477a-9dde-4f7bcb182771" xlink:to="loc_us-gaap_PreferredStockLiquidationPreferenceValue_77eb053c-8be4-4567-b1ad-cfe58fe7e273" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_PreferredStockBLiquidationPreferenceValue_3ed2d390-8df2-4e07-9003-547be56e191b" xlink:href="agnc-20220331.xsd#agnc_PreferredStockBLiquidationPreferenceValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FinancialInstrumentsOwnedAndPledgedAsCollateralLineItems_b5204d86-dcdf-477a-9dde-4f7bcb182771" xlink:to="loc_agnc_PreferredStockBLiquidationPreferenceValue_3ed2d390-8df2-4e07-9003-547be56e191b" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PreferredStockSharesOutstanding_fcea4b0b-92c1-456f-818e-98fe488e6bc6" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_PreferredStockSharesOutstanding"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FinancialInstrumentsOwnedAndPledgedAsCollateralLineItems_b5204d86-dcdf-477a-9dde-4f7bcb182771" xlink:to="loc_us-gaap_PreferredStockSharesOutstanding_fcea4b0b-92c1-456f-818e-98fe488e6bc6" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_PreferredStockCLiquidationPreferenceValue_1490efd9-7dca-4986-9aa8-17aae0c835f4" xlink:href="agnc-20220331.xsd#agnc_PreferredStockCLiquidationPreferenceValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FinancialInstrumentsOwnedAndPledgedAsCollateralLineItems_b5204d86-dcdf-477a-9dde-4f7bcb182771" xlink:to="loc_agnc_PreferredStockCLiquidationPreferenceValue_1490efd9-7dca-4986-9aa8-17aae0c835f4" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_PreferredStockDLiquidationPreferenceValue_6e97feed-1b08-4068-8b14-e22a13cef4c1" xlink:href="agnc-20220331.xsd#agnc_PreferredStockDLiquidationPreferenceValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FinancialInstrumentsOwnedAndPledgedAsCollateralLineItems_b5204d86-dcdf-477a-9dde-4f7bcb182771" xlink:to="loc_agnc_PreferredStockDLiquidationPreferenceValue_6e97feed-1b08-4068-8b14-e22a13cef4c1" xlink:type="arc" order="7"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CommonStockParOrStatedValuePerShare_d56ed420-ab1f-4873-88e2-6d4d6e6f6b82" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_CommonStockParOrStatedValuePerShare"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FinancialInstrumentsOwnedAndPledgedAsCollateralLineItems_b5204d86-dcdf-477a-9dde-4f7bcb182771" xlink:to="loc_us-gaap_CommonStockParOrStatedValuePerShare_d56ed420-ab1f-4873-88e2-6d4d6e6f6b82" xlink:type="arc" order="8"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CommonStockSharesAuthorized_7957f806-6a8c-47f4-9b9d-3a0f5ab9c6fc" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_CommonStockSharesAuthorized"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FinancialInstrumentsOwnedAndPledgedAsCollateralLineItems_b5204d86-dcdf-477a-9dde-4f7bcb182771" xlink:to="loc_us-gaap_CommonStockSharesAuthorized_7957f806-6a8c-47f4-9b9d-3a0f5ab9c6fc" xlink:type="arc" order="9"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CommonStockSharesIssued_102d3e63-7ba2-49c6-a593-8ea798b42798" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_CommonStockSharesIssued"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FinancialInstrumentsOwnedAndPledgedAsCollateralLineItems_b5204d86-dcdf-477a-9dde-4f7bcb182771" xlink:to="loc_us-gaap_CommonStockSharesIssued_102d3e63-7ba2-49c6-a593-8ea798b42798" xlink:type="arc" order="10"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CommonStockSharesOutstanding_6eb37bcf-68b0-4cc6-85b0-5013ec252a9b" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_CommonStockSharesOutstanding"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FinancialInstrumentsOwnedAndPledgedAsCollateralLineItems_b5204d86-dcdf-477a-9dde-4f7bcb182771" xlink:to="loc_us-gaap_CommonStockSharesOutstanding_6eb37bcf-68b0-4cc6-85b0-5013ec252a9b" xlink:type="arc" order="11"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_Security12bTitle_63df6c53-11f7-4aca-b1d2-7bf17bc025b5" xlink:href="https://xbrl.sec.gov/dei/2021q4/dei-2021q4.xsd#dei_Security12bTitle"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FinancialInstrumentsOwnedAndPledgedAsCollateralLineItems_b5204d86-dcdf-477a-9dde-4f7bcb182771" xlink:to="loc_dei_Security12bTitle_63df6c53-11f7-4aca-b1d2-7bf17bc025b5" xlink:type="arc" order="12"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_PledgedFinancialInstrumentsSecurities_2f4175a3-a5f8-40f3-bfec-0fbffd7234bc" xlink:href="agnc-20220331.xsd#agnc_PledgedFinancialInstrumentsSecurities"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FinancialInstrumentsOwnedAndPledgedAsCollateralLineItems_b5204d86-dcdf-477a-9dde-4f7bcb182771" xlink:to="loc_agnc_PledgedFinancialInstrumentsSecurities_2f4175a3-a5f8-40f3-bfec-0fbffd7234bc" xlink:type="arc" order="13"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FinancialInstrumentsOwnedAndPledgedAsCollateralTable_64af44c1-9660-4805-a972-3cb318da9b1a" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FinancialInstrumentsOwnedAndPledgedAsCollateralTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_FinancialInstrumentsOwnedAndPledgedAsCollateralLineItems_b5204d86-dcdf-477a-9dde-4f7bcb182771" xlink:to="loc_us-gaap_FinancialInstrumentsOwnedAndPledgedAsCollateralTable_64af44c1-9660-4805-a972-3cb318da9b1a" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueByAssetClassAxis_984f528a-0d36-4486-a1c6-6153b1ef1f68" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FairValueByAssetClassAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_FinancialInstrumentsOwnedAndPledgedAsCollateralTable_64af44c1-9660-4805-a972-3cb318da9b1a" xlink:to="loc_us-gaap_FairValueByAssetClassAxis_984f528a-0d36-4486-a1c6-6153b1ef1f68" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueAssetsMeasuredOnRecurringBasisUnobservableInputReconciliationByAssetClassDomain_984f528a-0d36-4486-a1c6-6153b1ef1f68_default" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FairValueAssetsMeasuredOnRecurringBasisUnobservableInputReconciliationByAssetClassDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_FairValueByAssetClassAxis_984f528a-0d36-4486-a1c6-6153b1ef1f68" xlink:to="loc_us-gaap_FairValueAssetsMeasuredOnRecurringBasisUnobservableInputReconciliationByAssetClassDomain_984f528a-0d36-4486-a1c6-6153b1ef1f68_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueAssetsMeasuredOnRecurringBasisUnobservableInputReconciliationByAssetClassDomain_670a0dba-c18b-4cf9-9135-496b14b0013a" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FairValueAssetsMeasuredOnRecurringBasisUnobservableInputReconciliationByAssetClassDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_FairValueByAssetClassAxis_984f528a-0d36-4486-a1c6-6153b1ef1f68" xlink:to="loc_us-gaap_FairValueAssetsMeasuredOnRecurringBasisUnobservableInputReconciliationByAssetClassDomain_670a0dba-c18b-4cf9-9135-496b14b0013a" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AssetPledgedAsCollateralMember_e114c565-7bba-4149-8788-80f41757d146" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AssetPledgedAsCollateralMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FairValueAssetsMeasuredOnRecurringBasisUnobservableInputReconciliationByAssetClassDomain_670a0dba-c18b-4cf9-9135-496b14b0013a" xlink:to="loc_us-gaap_AssetPledgedAsCollateralMember_e114c565-7bba-4149-8788-80f41757d146" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_UnderlyingAssetClassAxis_cdeebebb-107c-443e-ba3f-66727c5f370b" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_UnderlyingAssetClassAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_FinancialInstrumentsOwnedAndPledgedAsCollateralTable_64af44c1-9660-4805-a972-3cb318da9b1a" xlink:to="loc_us-gaap_UnderlyingAssetClassAxis_cdeebebb-107c-443e-ba3f-66727c5f370b" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_UnderlyingAssetClassDomain_cdeebebb-107c-443e-ba3f-66727c5f370b_default" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_UnderlyingAssetClassDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_UnderlyingAssetClassAxis_cdeebebb-107c-443e-ba3f-66727c5f370b" xlink:to="loc_us-gaap_UnderlyingAssetClassDomain_cdeebebb-107c-443e-ba3f-66727c5f370b_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_UnderlyingAssetClassDomain_1a637ad9-b87e-45a7-b2e0-71d3e5f270f4" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_UnderlyingAssetClassDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_UnderlyingAssetClassAxis_cdeebebb-107c-443e-ba3f-66727c5f370b" xlink:to="loc_us-gaap_UnderlyingAssetClassDomain_1a637ad9-b87e-45a7-b2e0-71d3e5f270f4" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AgencySecuritiesMember_f5e4e3c4-b0a9-44d0-adf1-697b4ce61330" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AgencySecuritiesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_UnderlyingAssetClassDomain_1a637ad9-b87e-45a7-b2e0-71d3e5f270f4" xlink:to="loc_us-gaap_AgencySecuritiesMember_f5e4e3c4-b0a9-44d0-adf1-697b4ce61330" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_CreditRiskTransferSecuritiesMember_ec2838f4-c875-403f-8f30-999dd5684370" xlink:href="agnc-20220331.xsd#agnc_CreditRiskTransferSecuritiesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_UnderlyingAssetClassDomain_1a637ad9-b87e-45a7-b2e0-71d3e5f270f4" xlink:to="loc_agnc_CreditRiskTransferSecuritiesMember_ec2838f4-c875-403f-8f30-999dd5684370" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_MortgageBackedSecuritiesIssuedByPrivateEnterprisesMember_1b09fccb-c62f-4130-9520-0f5a991ad092" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_MortgageBackedSecuritiesIssuedByPrivateEnterprisesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_UnderlyingAssetClassDomain_1a637ad9-b87e-45a7-b2e0-71d3e5f270f4" xlink:to="loc_us-gaap_MortgageBackedSecuritiesIssuedByPrivateEnterprisesMember_1b09fccb-c62f-4130-9520-0f5a991ad092" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_USTreasurySecuritiesMember_cc4b6053-22d5-41d0-a6c4-46e5a2ddd9e5" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_USTreasurySecuritiesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_UnderlyingAssetClassDomain_1a637ad9-b87e-45a7-b2e0-71d3e5f270f4" xlink:to="loc_us-gaap_USTreasurySecuritiesMember_cc4b6053-22d5-41d0-a6c4-46e5a2ddd9e5" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_ReceivableforsecuritiessoldMember_1b50e7d3-389a-41c3-a2c4-a970ff81a213" xlink:href="agnc-20220331.xsd#agnc_ReceivableforsecuritiessoldMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_UnderlyingAssetClassDomain_1a637ad9-b87e-45a7-b2e0-71d3e5f270f4" xlink:to="loc_agnc_ReceivableforsecuritiessoldMember_1b50e7d3-389a-41c3-a2c4-a970ff81a213" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StatementClassOfStockAxis_13e15825-7e88-445d-a9cd-c741d13df696" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_StatementClassOfStockAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_FinancialInstrumentsOwnedAndPledgedAsCollateralTable_64af44c1-9660-4805-a972-3cb318da9b1a" xlink:to="loc_us-gaap_StatementClassOfStockAxis_13e15825-7e88-445d-a9cd-c741d13df696" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ClassOfStockDomain_13e15825-7e88-445d-a9cd-c741d13df696_default" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ClassOfStockDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_StatementClassOfStockAxis_13e15825-7e88-445d-a9cd-c741d13df696" xlink:to="loc_us-gaap_ClassOfStockDomain_13e15825-7e88-445d-a9cd-c741d13df696_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ClassOfStockDomain_9808e404-3187-493d-9982-e1ca5d30eb93" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ClassOfStockDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_StatementClassOfStockAxis_13e15825-7e88-445d-a9cd-c741d13df696" xlink:to="loc_us-gaap_ClassOfStockDomain_9808e404-3187-493d-9982-e1ca5d30eb93" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CommonStockMember_4f1d85c8-2605-4d7a-8b19-537a87d08df9" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_CommonStockMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockDomain_9808e404-3187-493d-9982-e1ca5d30eb93" xlink:to="loc_us-gaap_CommonStockMember_4f1d85c8-2605-4d7a-8b19-537a87d08df9" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_Depositoryshareseachrepresentinga11000thinterestinashareof7.000SeriesCFixedtoFloatingRateCumulativeRedeemablePreferredStockMember_8f03ea69-9d84-49b0-a03a-c4269e6b41d8" xlink:href="agnc-20220331.xsd#agnc_Depositoryshareseachrepresentinga11000thinterestinashareof7.000SeriesCFixedtoFloatingRateCumulativeRedeemablePreferredStockMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockDomain_9808e404-3187-493d-9982-e1ca5d30eb93" xlink:to="loc_agnc_Depositoryshareseachrepresentinga11000thinterestinashareof7.000SeriesCFixedtoFloatingRateCumulativeRedeemablePreferredStockMember_8f03ea69-9d84-49b0-a03a-c4269e6b41d8" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_Depositoryshareseachrepresentinga11000thinterestinashareof6.875SeriesDFixedtoFloatingRateCumulativeRedeemablePreferredStockMember_a61ac82c-eb8b-4c4b-b291-b33e61ea16fa" xlink:href="agnc-20220331.xsd#agnc_Depositoryshareseachrepresentinga11000thinterestinashareof6.875SeriesDFixedtoFloatingRateCumulativeRedeemablePreferredStockMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockDomain_9808e404-3187-493d-9982-e1ca5d30eb93" xlink:to="loc_agnc_Depositoryshareseachrepresentinga11000thinterestinashareof6.875SeriesDFixedtoFloatingRateCumulativeRedeemablePreferredStockMember_a61ac82c-eb8b-4c4b-b291-b33e61ea16fa" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_Depositoryshareseachrepresentinga11000thinterestinashareof6.500SeriesEFixedtoFloatingRateCumulativeRedeemablePreferredStockMember_da4fca28-80b2-4313-9473-2147db675c2b" xlink:href="agnc-20220331.xsd#agnc_Depositoryshareseachrepresentinga11000thinterestinashareof6.500SeriesEFixedtoFloatingRateCumulativeRedeemablePreferredStockMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockDomain_9808e404-3187-493d-9982-e1ca5d30eb93" xlink:to="loc_agnc_Depositoryshareseachrepresentinga11000thinterestinashareof6.500SeriesEFixedtoFloatingRateCumulativeRedeemablePreferredStockMember_da4fca28-80b2-4313-9473-2147db675c2b" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_Depositaryshareseachrepresentinga11000thinterestinashareof6.125SeriesFFixedtoFloatingRateCumulativeRedeemablePreferredStockMember_b5221f10-16bc-4cea-8937-84aca43cbf8d" xlink:href="agnc-20220331.xsd#agnc_Depositaryshareseachrepresentinga11000thinterestinashareof6.125SeriesFFixedtoFloatingRateCumulativeRedeemablePreferredStockMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockDomain_9808e404-3187-493d-9982-e1ca5d30eb93" xlink:to="loc_agnc_Depositaryshareseachrepresentinga11000thinterestinashareof6.125SeriesFFixedtoFloatingRateCumulativeRedeemablePreferredStockMember_b5221f10-16bc-4cea-8937-84aca43cbf8d" xlink:type="arc" order="4"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.agnc.com/role/ConsolidatedStatementsOfComprehensiveIncome" xlink:type="simple" xlink:href="agnc-20220331.xsd#ConsolidatedStatementsOfComprehensiveIncome"/>
  <link:definitionLink xlink:role="http://www.agnc.com/role/ConsolidatedStatementsOfComprehensiveIncome" xlink:type="extended" id="i8fb9dbea1b224e4caba3c481d61632f0_ConsolidatedStatementsOfComprehensiveIncome">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StatementLineItems_c8388fd3-acfc-49f9-9167-ddad29b63061" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_StatementLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_Issuancecostsofredeemedpreferredstock_9be72bd5-604e-4f04-8bf6-ce90618b2ca4" xlink:href="agnc-20220331.xsd#agnc_Issuancecostsofredeemedpreferredstock"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_c8388fd3-acfc-49f9-9167-ddad29b63061" xlink:to="loc_agnc_Issuancecostsofredeemedpreferredstock_9be72bd5-604e-4f04-8bf6-ce90618b2ca4" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CommonStockDividendsPerShareDeclared_b1fca5e5-0496-4305-b6b0-c63c358085e5" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_CommonStockDividendsPerShareDeclared"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_c8388fd3-acfc-49f9-9167-ddad29b63061" xlink:to="loc_us-gaap_CommonStockDividendsPerShareDeclared_b1fca5e5-0496-4305-b6b0-c63c358085e5" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_GainLossOnSalesOfMortgageBackedSecuritiesMBS_b7654d7b-0f2d-4095-8fe1-cf0e2f782671" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_GainLossOnSalesOfMortgageBackedSecuritiesMBS"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_c8388fd3-acfc-49f9-9167-ddad29b63061" xlink:to="loc_us-gaap_GainLossOnSalesOfMortgageBackedSecuritiesMBS_b7654d7b-0f2d-4095-8fe1-cf0e2f782671" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_Unrealizedgainlossoninvestmentsecuritiesmeasuredatfairvaluethroughnetincomenet_baa8c8fb-bb99-4e10-ad71-da60b171c0d6" xlink:href="agnc-20220331.xsd#agnc_Unrealizedgainlossoninvestmentsecuritiesmeasuredatfairvaluethroughnetincomenet"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_c8388fd3-acfc-49f9-9167-ddad29b63061" xlink:to="loc_agnc_Unrealizedgainlossoninvestmentsecuritiesmeasuredatfairvaluethroughnetincomenet_baa8c8fb-bb99-4e10-ad71-da60b171c0d6" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_Gainlossonderivativeinstrumentsandothersecuritiesnet_a5461477-f2b6-492d-aa74-e8910bb3fb67" xlink:href="agnc-20220331.xsd#agnc_Gainlossonderivativeinstrumentsandothersecuritiesnet"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_c8388fd3-acfc-49f9-9167-ddad29b63061" xlink:to="loc_agnc_Gainlossonderivativeinstrumentsandothersecuritiesnet_a5461477-f2b6-492d-aa74-e8910bb3fb67" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_ManagementFeeIncome_cad53b6c-4ed2-4ff1-b1bd-8245963ba62d" xlink:href="agnc-20220331.xsd#agnc_ManagementFeeIncome"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_c8388fd3-acfc-49f9-9167-ddad29b63061" xlink:to="loc_agnc_ManagementFeeIncome_cad53b6c-4ed2-4ff1-b1bd-8245963ba62d" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_NonoperatingIncomeExpense_2762e9b9-c52a-4f86-a669-6136bf0ae01f" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_NonoperatingIncomeExpense"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_c8388fd3-acfc-49f9-9167-ddad29b63061" xlink:to="loc_us-gaap_NonoperatingIncomeExpense_2762e9b9-c52a-4f86-a669-6136bf0ae01f" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_InterestIncomeSecuritiesMortgageBacked_58ed0759-2b7c-4a84-8854-29e64edebed1" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_InterestIncomeSecuritiesMortgageBacked"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_c8388fd3-acfc-49f9-9167-ddad29b63061" xlink:to="loc_us-gaap_InterestIncomeSecuritiesMortgageBacked_58ed0759-2b7c-4a84-8854-29e64edebed1" xlink:type="arc" order="7"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_InterestExpense_81b19722-d65c-406b-83ea-dc5381ff4f48" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_InterestExpense"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_c8388fd3-acfc-49f9-9167-ddad29b63061" xlink:to="loc_us-gaap_InterestExpense_81b19722-d65c-406b-83ea-dc5381ff4f48" xlink:type="arc" order="8"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_InterestIncomeExpenseNet_744ef89f-33e3-42bc-9ba4-dfa1ffadf1bd" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_InterestIncomeExpenseNet"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_c8388fd3-acfc-49f9-9167-ddad29b63061" xlink:to="loc_us-gaap_InterestIncomeExpenseNet_744ef89f-33e3-42bc-9ba4-dfa1ffadf1bd" xlink:type="arc" order="9"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LaborAndRelatedExpense_ba38a6f3-b1d3-4526-b92a-f23bbe065db1" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_LaborAndRelatedExpense"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_c8388fd3-acfc-49f9-9167-ddad29b63061" xlink:to="loc_us-gaap_LaborAndRelatedExpense_ba38a6f3-b1d3-4526-b92a-f23bbe065db1" xlink:type="arc" order="10"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_GeneralAndAdministrativeExpense_3be0ac43-5578-493b-b1fc-65891f3c8ee2" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_GeneralAndAdministrativeExpense"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_c8388fd3-acfc-49f9-9167-ddad29b63061" xlink:to="loc_us-gaap_GeneralAndAdministrativeExpense_3be0ac43-5578-493b-b1fc-65891f3c8ee2" xlink:type="arc" order="11"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OperatingExpenses_d3f999fa-dd6b-4003-93f8-6b39440639bf" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_OperatingExpenses"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_c8388fd3-acfc-49f9-9167-ddad29b63061" xlink:to="loc_us-gaap_OperatingExpenses_d3f999fa-dd6b-4003-93f8-6b39440639bf" xlink:type="arc" order="12"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_NetIncomeLoss_6547d958-316b-4afa-a100-5fd469fb2a6e" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_NetIncomeLoss"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_c8388fd3-acfc-49f9-9167-ddad29b63061" xlink:to="loc_us-gaap_NetIncomeLoss_6547d958-316b-4afa-a100-5fd469fb2a6e" xlink:type="arc" order="13"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PreferredStockDividendsIncomeStatementImpact_41b1f71c-6cca-4079-9a27-54408c8b4fb7" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_PreferredStockDividendsIncomeStatementImpact"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_c8388fd3-acfc-49f9-9167-ddad29b63061" xlink:to="loc_us-gaap_PreferredStockDividendsIncomeStatementImpact_41b1f71c-6cca-4079-9a27-54408c8b4fb7" xlink:type="arc" order="14"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_NetIncomeLossAvailableToCommonStockholdersBasic_f8a660b2-19d2-4c12-990c-de1637a29672" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_NetIncomeLossAvailableToCommonStockholdersBasic"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_c8388fd3-acfc-49f9-9167-ddad29b63061" xlink:to="loc_us-gaap_NetIncomeLossAvailableToCommonStockholdersBasic_f8a660b2-19d2-4c12-990c-de1637a29672" xlink:type="arc" order="15"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherComprehensiveIncomeUnrealizedHoldingGainLossOnSecuritiesArisingDuringPeriodNetOfTax_ff37ed2f-d8e5-4c3b-918a-51911b7718fd" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_OtherComprehensiveIncomeUnrealizedHoldingGainLossOnSecuritiesArisingDuringPeriodNetOfTax"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_c8388fd3-acfc-49f9-9167-ddad29b63061" xlink:to="loc_us-gaap_OtherComprehensiveIncomeUnrealizedHoldingGainLossOnSecuritiesArisingDuringPeriodNetOfTax_ff37ed2f-d8e5-4c3b-918a-51911b7718fd" xlink:type="arc" order="16"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ComprehensiveIncomeNetOfTax_2e1730c1-a36c-4676-8c20-f48d8073580e" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ComprehensiveIncomeNetOfTax"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_c8388fd3-acfc-49f9-9167-ddad29b63061" xlink:to="loc_us-gaap_ComprehensiveIncomeNetOfTax_2e1730c1-a36c-4676-8c20-f48d8073580e" xlink:type="arc" order="17"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_ComprehensiveIncomeAvailableToCommonShareholders_070ca951-4cda-4c48-a23e-e6a9c572b1f0" xlink:href="agnc-20220331.xsd#agnc_ComprehensiveIncomeAvailableToCommonShareholders"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_c8388fd3-acfc-49f9-9167-ddad29b63061" xlink:to="loc_agnc_ComprehensiveIncomeAvailableToCommonShareholders_070ca951-4cda-4c48-a23e-e6a9c572b1f0" xlink:type="arc" order="18"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_WeightedAverageNumberOfSharesOutstandingBasic_b5b4ea29-6eeb-494f-95ef-9cac171b184e" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_WeightedAverageNumberOfSharesOutstandingBasic"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_c8388fd3-acfc-49f9-9167-ddad29b63061" xlink:to="loc_us-gaap_WeightedAverageNumberOfSharesOutstandingBasic_b5b4ea29-6eeb-494f-95ef-9cac171b184e" xlink:type="arc" order="19"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_WeightedAverageNumberOfDilutedSharesOutstanding_635c8f61-b39e-407f-8384-891e9def459b" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_WeightedAverageNumberOfDilutedSharesOutstanding"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_c8388fd3-acfc-49f9-9167-ddad29b63061" xlink:to="loc_us-gaap_WeightedAverageNumberOfDilutedSharesOutstanding_635c8f61-b39e-407f-8384-891e9def459b" xlink:type="arc" order="20"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EarningsPerShareBasic_01131215-60f1-4eea-b477-2ef5bcb28688" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_EarningsPerShareBasic"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_c8388fd3-acfc-49f9-9167-ddad29b63061" xlink:to="loc_us-gaap_EarningsPerShareBasic_01131215-60f1-4eea-b477-2ef5bcb28688" xlink:type="arc" order="21"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EarningsPerShareDiluted_b0122fdd-9635-4a12-9446-3404e017670b" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_EarningsPerShareDiluted"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_c8388fd3-acfc-49f9-9167-ddad29b63061" xlink:to="loc_us-gaap_EarningsPerShareDiluted_b0122fdd-9635-4a12-9446-3404e017670b" xlink:type="arc" order="22"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StatementTable_d8dd1d5e-cfe8-4ee9-bfa1-067427bf77d2" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_StatementTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_StatementLineItems_c8388fd3-acfc-49f9-9167-ddad29b63061" xlink:to="loc_us-gaap_StatementTable_d8dd1d5e-cfe8-4ee9-bfa1-067427bf77d2" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_StatementScenarioAxis_b2f03aae-a560-4e97-bd34-f5ded809c4ae" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_StatementScenarioAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_StatementTable_d8dd1d5e-cfe8-4ee9-bfa1-067427bf77d2" xlink:to="loc_srt_StatementScenarioAxis_b2f03aae-a560-4e97-bd34-f5ded809c4ae" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ScenarioUnspecifiedDomain_b2f03aae-a560-4e97-bd34-f5ded809c4ae_default" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_ScenarioUnspecifiedDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_StatementScenarioAxis_b2f03aae-a560-4e97-bd34-f5ded809c4ae" xlink:to="loc_srt_ScenarioUnspecifiedDomain_b2f03aae-a560-4e97-bd34-f5ded809c4ae_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ScenarioUnspecifiedDomain_c5534e2c-e8e8-4958-9cdb-5fd7912ef06b" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_ScenarioUnspecifiedDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_StatementScenarioAxis_b2f03aae-a560-4e97-bd34-f5ded809c4ae" xlink:to="loc_srt_ScenarioUnspecifiedDomain_c5534e2c-e8e8-4958-9cdb-5fd7912ef06b" xlink:type="arc" order="1"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.agnc.com/role/ConsolidatedStatementofStockholdersEquity" xlink:type="simple" xlink:href="agnc-20220331.xsd#ConsolidatedStatementofStockholdersEquity"/>
  <link:definitionLink xlink:role="http://www.agnc.com/role/ConsolidatedStatementofStockholdersEquity" xlink:type="extended" id="ifecfd08115a34982aea5bb0649e91c09_ConsolidatedStatementofStockholdersEquity">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StatementLineItems_abdbe629-246a-44d9-9ace-cc4afee1f9af" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_StatementLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockholdersEquity_700255e2-4bc2-4c00-a50e-a9fb4c93c69c" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_StockholdersEquity"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_abdbe629-246a-44d9-9ace-cc4afee1f9af" xlink:to="loc_us-gaap_StockholdersEquity_700255e2-4bc2-4c00-a50e-a9fb4c93c69c" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CommonStockSharesOutstanding_794d6586-a9b9-46a0-b10c-b02b0134eb17" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_CommonStockSharesOutstanding"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_abdbe629-246a-44d9-9ace-cc4afee1f9af" xlink:to="loc_us-gaap_CommonStockSharesOutstanding_794d6586-a9b9-46a0-b10c-b02b0134eb17" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_NetIncomeLoss_f266bb77-d011-4ab7-acfc-390bba45f87c" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_NetIncomeLoss"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_abdbe629-246a-44d9-9ace-cc4afee1f9af" xlink:to="loc_us-gaap_NetIncomeLoss_f266bb77-d011-4ab7-acfc-390bba45f87c" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherComprehensiveIncomeLossNetOfTaxPeriodIncreaseDecreaseAbstract_1d32aa0c-2d6d-497f-bbf6-a32c6e29ddbf" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_OtherComprehensiveIncomeLossNetOfTaxPeriodIncreaseDecreaseAbstract"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_abdbe629-246a-44d9-9ace-cc4afee1f9af" xlink:to="loc_us-gaap_OtherComprehensiveIncomeLossNetOfTaxPeriodIncreaseDecreaseAbstract_1d32aa0c-2d6d-497f-bbf6-a32c6e29ddbf" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherComprehensiveIncomeUnrealizedHoldingGainLossOnSecuritiesArisingDuringPeriodNetOfTax_7f2ce102-58e7-4d51-aea5-0a96e680198d" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_OtherComprehensiveIncomeUnrealizedHoldingGainLossOnSecuritiesArisingDuringPeriodNetOfTax"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_OtherComprehensiveIncomeLossNetOfTaxPeriodIncreaseDecreaseAbstract_1d32aa0c-2d6d-497f-bbf6-a32c6e29ddbf" xlink:to="loc_us-gaap_OtherComprehensiveIncomeUnrealizedHoldingGainLossOnSecuritiesArisingDuringPeriodNetOfTax_7f2ce102-58e7-4d51-aea5-0a96e680198d" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherComprehensiveIncomeUnrealizedGainLossOnDerivativesArisingDuringPeriodNetOfTax_83675623-a2cd-4280-b49d-54d1c8b2d6fb" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_OtherComprehensiveIncomeUnrealizedGainLossOnDerivativesArisingDuringPeriodNetOfTax"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_OtherComprehensiveIncomeLossNetOfTaxPeriodIncreaseDecreaseAbstract_1d32aa0c-2d6d-497f-bbf6-a32c6e29ddbf" xlink:to="loc_us-gaap_OtherComprehensiveIncomeUnrealizedGainLossOnDerivativesArisingDuringPeriodNetOfTax_83675623-a2cd-4280-b49d-54d1c8b2d6fb" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockIssuedDuringPeriodSharesShareBasedCompensationGross_374d3e6c-1eaf-49f8-8a30-a837a8ffc192" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_StockIssuedDuringPeriodSharesShareBasedCompensationGross"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_abdbe629-246a-44d9-9ace-cc4afee1f9af" xlink:to="loc_us-gaap_StockIssuedDuringPeriodSharesShareBasedCompensationGross_374d3e6c-1eaf-49f8-8a30-a837a8ffc192" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationAndExerciseOfStockOptions_0df96689-d567-4a7f-a5ce-e24479cf3330" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationAndExerciseOfStockOptions"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_abdbe629-246a-44d9-9ace-cc4afee1f9af" xlink:to="loc_us-gaap_AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationAndExerciseOfStockOptions_0df96689-d567-4a7f-a5ce-e24479cf3330" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockRepurchasedDuringPeriodShares_73e01629-253e-4eaa-8e27-63441335a468" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_StockRepurchasedDuringPeriodShares"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_abdbe629-246a-44d9-9ace-cc4afee1f9af" xlink:to="loc_us-gaap_StockRepurchasedDuringPeriodShares_73e01629-253e-4eaa-8e27-63441335a468" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ProceedsFromIssuanceOfPreferredStockAndPreferenceStock_c6599d56-d3e0-4747-be6b-9317a6492ec8" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ProceedsFromIssuanceOfPreferredStockAndPreferenceStock"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_abdbe629-246a-44d9-9ace-cc4afee1f9af" xlink:to="loc_us-gaap_ProceedsFromIssuanceOfPreferredStockAndPreferenceStock_c6599d56-d3e0-4747-be6b-9317a6492ec8" xlink:type="arc" order="7"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockRedeemedOrCalledDuringPeriodValue_67e82788-7d24-44a4-8af5-5b65421879ac" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_StockRedeemedOrCalledDuringPeriodValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_abdbe629-246a-44d9-9ace-cc4afee1f9af" xlink:to="loc_us-gaap_StockRedeemedOrCalledDuringPeriodValue_67e82788-7d24-44a4-8af5-5b65421879ac" xlink:type="arc" order="8"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_Issuancecostsofredeemedpreferredstock_23fe6aed-2ab0-45de-8760-a4b7690417ef" xlink:href="agnc-20220331.xsd#agnc_Issuancecostsofredeemedpreferredstock"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_abdbe629-246a-44d9-9ace-cc4afee1f9af" xlink:to="loc_agnc_Issuancecostsofredeemedpreferredstock_23fe6aed-2ab0-45de-8760-a4b7690417ef" xlink:type="arc" order="9"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockIssuedDuringPeriodSharesNewIssues_62c7c63c-b8fc-4311-b266-c1285e0c5b02" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_StockIssuedDuringPeriodSharesNewIssues"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_abdbe629-246a-44d9-9ace-cc4afee1f9af" xlink:to="loc_us-gaap_StockIssuedDuringPeriodSharesNewIssues_62c7c63c-b8fc-4311-b266-c1285e0c5b02" xlink:type="arc" order="10"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockIssuedDuringPeriodValueNewIssues_fd425bca-fcbf-4e25-bd00-062e5082270e" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_StockIssuedDuringPeriodValueNewIssues"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_abdbe629-246a-44d9-9ace-cc4afee1f9af" xlink:to="loc_us-gaap_StockIssuedDuringPeriodValueNewIssues_fd425bca-fcbf-4e25-bd00-062e5082270e" xlink:type="arc" order="11"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockRepurchasedDuringPeriodValue_2877bdef-13e5-4dce-941d-16b907996aa7" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_StockRepurchasedDuringPeriodValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_abdbe629-246a-44d9-9ace-cc4afee1f9af" xlink:to="loc_us-gaap_StockRepurchasedDuringPeriodValue_2877bdef-13e5-4dce-941d-16b907996aa7" xlink:type="arc" order="12"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PaymentsForRepurchaseOfCommonStock_5f5645f7-0374-4c44-aa53-ac17483dd570" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_PaymentsForRepurchaseOfCommonStock"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_abdbe629-246a-44d9-9ace-cc4afee1f9af" xlink:to="loc_us-gaap_PaymentsForRepurchaseOfCommonStock_5f5645f7-0374-4c44-aa53-ac17483dd570" xlink:type="arc" order="13"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DividendsPreferredStockCash_2b36dbeb-bc63-41e3-98cd-71ae962ea695" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DividendsPreferredStockCash"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_abdbe629-246a-44d9-9ace-cc4afee1f9af" xlink:to="loc_us-gaap_DividendsPreferredStockCash_2b36dbeb-bc63-41e3-98cd-71ae962ea695" xlink:type="arc" order="14"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DividendsCommonStockCash_f8a5ea16-42dd-480a-876d-805ab3c76617" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DividendsCommonStockCash"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_abdbe629-246a-44d9-9ace-cc4afee1f9af" xlink:to="loc_us-gaap_DividendsCommonStockCash_f8a5ea16-42dd-480a-876d-805ab3c76617" xlink:type="arc" order="15"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockholdersEquity_597c2f20-b920-4d53-b5fa-c77797357036" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_StockholdersEquity"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CommonStockSharesOutstanding_e263b726-55c8-48f1-a796-11dbe75ee69d" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_CommonStockSharesOutstanding"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StatementTable_83d32544-3612-4913-b8e2-afc67998b7e7" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_StatementTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_StatementLineItems_abdbe629-246a-44d9-9ace-cc4afee1f9af" xlink:to="loc_us-gaap_StatementTable_83d32544-3612-4913-b8e2-afc67998b7e7" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StatementClassOfStockAxis_3f35adb2-2f91-4085-9a00-efaffd70e9af" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_StatementClassOfStockAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_StatementTable_83d32544-3612-4913-b8e2-afc67998b7e7" xlink:to="loc_us-gaap_StatementClassOfStockAxis_3f35adb2-2f91-4085-9a00-efaffd70e9af" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ClassOfStockDomain_3f35adb2-2f91-4085-9a00-efaffd70e9af_default" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ClassOfStockDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_StatementClassOfStockAxis_3f35adb2-2f91-4085-9a00-efaffd70e9af" xlink:to="loc_us-gaap_ClassOfStockDomain_3f35adb2-2f91-4085-9a00-efaffd70e9af_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ClassOfStockDomain_2a403683-8b89-4a84-85ec-ad7a8c06a240" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ClassOfStockDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_StatementClassOfStockAxis_3f35adb2-2f91-4085-9a00-efaffd70e9af" xlink:to="loc_us-gaap_ClassOfStockDomain_2a403683-8b89-4a84-85ec-ad7a8c06a240" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SeriesAPreferredStockMember_cdd1086d-aec0-4246-a9d7-ed09ac36e8d8" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_SeriesAPreferredStockMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockDomain_2a403683-8b89-4a84-85ec-ad7a8c06a240" xlink:to="loc_us-gaap_SeriesAPreferredStockMember_cdd1086d-aec0-4246-a9d7-ed09ac36e8d8" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SeriesBPreferredStockMember_bcc5f963-3d56-4e16-89e7-9775dd6f6ff7" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_SeriesBPreferredStockMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockDomain_2a403683-8b89-4a84-85ec-ad7a8c06a240" xlink:to="loc_us-gaap_SeriesBPreferredStockMember_bcc5f963-3d56-4e16-89e7-9775dd6f6ff7" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SeriesCPreferredStockMember_627a2fe8-cbb9-455c-b3cd-5f043699c49d" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_SeriesCPreferredStockMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockDomain_2a403683-8b89-4a84-85ec-ad7a8c06a240" xlink:to="loc_us-gaap_SeriesCPreferredStockMember_627a2fe8-cbb9-455c-b3cd-5f043699c49d" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SeriesDPreferredStockMember_d163abb7-dc32-4d5a-a8d1-8e105ca27609" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_SeriesDPreferredStockMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockDomain_2a403683-8b89-4a84-85ec-ad7a8c06a240" xlink:to="loc_us-gaap_SeriesDPreferredStockMember_d163abb7-dc32-4d5a-a8d1-8e105ca27609" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StatementEquityComponentsAxis_546eb359-1a33-43ca-aee2-6ea55e1c18ce" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_StatementEquityComponentsAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_StatementTable_83d32544-3612-4913-b8e2-afc67998b7e7" xlink:to="loc_us-gaap_StatementEquityComponentsAxis_546eb359-1a33-43ca-aee2-6ea55e1c18ce" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EquityComponentDomain_546eb359-1a33-43ca-aee2-6ea55e1c18ce_default" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_EquityComponentDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_StatementEquityComponentsAxis_546eb359-1a33-43ca-aee2-6ea55e1c18ce" xlink:to="loc_us-gaap_EquityComponentDomain_546eb359-1a33-43ca-aee2-6ea55e1c18ce_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EquityComponentDomain_88622d92-4a87-4583-9c74-23e75d35ab2f" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_EquityComponentDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_StatementEquityComponentsAxis_546eb359-1a33-43ca-aee2-6ea55e1c18ce" xlink:to="loc_us-gaap_EquityComponentDomain_88622d92-4a87-4583-9c74-23e75d35ab2f" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PreferredStockMember_7704b498-ae2e-44ea-8997-eee4182aeb6a" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_PreferredStockMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EquityComponentDomain_88622d92-4a87-4583-9c74-23e75d35ab2f" xlink:to="loc_us-gaap_PreferredStockMember_7704b498-ae2e-44ea-8997-eee4182aeb6a" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CommonStockMember_96a9f0e4-177e-4459-a48a-128ea469377b" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_CommonStockMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EquityComponentDomain_88622d92-4a87-4583-9c74-23e75d35ab2f" xlink:to="loc_us-gaap_CommonStockMember_96a9f0e4-177e-4459-a48a-128ea469377b" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AdditionalPaidInCapitalMember_a1c54cd8-afc1-4551-af66-044cb9363483" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AdditionalPaidInCapitalMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EquityComponentDomain_88622d92-4a87-4583-9c74-23e75d35ab2f" xlink:to="loc_us-gaap_AdditionalPaidInCapitalMember_a1c54cd8-afc1-4551-af66-044cb9363483" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RetainedEarningsMember_0097ee60-57f5-4003-9467-2ed0384d4cf3" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_RetainedEarningsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EquityComponentDomain_88622d92-4a87-4583-9c74-23e75d35ab2f" xlink:to="loc_us-gaap_RetainedEarningsMember_0097ee60-57f5-4003-9467-2ed0384d4cf3" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AccumulatedOtherComprehensiveIncomeMember_2d916b3a-9c0f-4a04-b296-4031969d82a3" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AccumulatedOtherComprehensiveIncomeMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EquityComponentDomain_88622d92-4a87-4583-9c74-23e75d35ab2f" xlink:to="loc_us-gaap_AccumulatedOtherComprehensiveIncomeMember_2d916b3a-9c0f-4a04-b296-4031969d82a3" xlink:type="arc" order="4"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.agnc.com/role/SummaryofSignificantAccountingPoliciesPolicy" xlink:type="simple" xlink:href="agnc-20220331.xsd#SummaryofSignificantAccountingPoliciesPolicy"/>
  <link:definitionLink xlink:role="http://www.agnc.com/role/SummaryofSignificantAccountingPoliciesPolicy" xlink:type="extended" id="i269e5f19d9e8440a988ea494727b18a0_SummaryofSignificantAccountingPoliciesPolicy">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_NewAccountingPronouncementsOrChangeInAccountingPrincipleLineItems_a37f3f74-d74f-4a6d-8791-00324a535843" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_NewAccountingPronouncementsOrChangeInAccountingPrincipleLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_BasisOfPresentationAndSignificantAccountingPoliciesTextBlock_5f1e0f27-83fd-45ad-a653-e8a239609801" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_BasisOfPresentationAndSignificantAccountingPoliciesTextBlock"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_NewAccountingPronouncementsOrChangeInAccountingPrincipleLineItems_a37f3f74-d74f-4a6d-8791-00324a535843" xlink:to="loc_us-gaap_BasisOfPresentationAndSignificantAccountingPoliciesTextBlock_5f1e0f27-83fd-45ad-a653-e8a239609801" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_NewAccountingPronouncementsAndChangesInAccountingPrinciplesTextBlock_4c3599e6-b807-4ec8-b240-f324a1eb0139" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_NewAccountingPronouncementsAndChangesInAccountingPrinciplesTextBlock"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_NewAccountingPronouncementsOrChangeInAccountingPrincipleLineItems_a37f3f74-d74f-4a6d-8791-00324a535843" xlink:to="loc_us-gaap_NewAccountingPronouncementsAndChangesInAccountingPrinciplesTextBlock_4c3599e6-b807-4ec8-b240-f324a1eb0139" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_GoodwillAndIntangibleAssetsPolicyTextBlock_21d5b29c-3960-43d5-ab4a-dcf3557df2ef" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_GoodwillAndIntangibleAssetsPolicyTextBlock"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_NewAccountingPronouncementsOrChangeInAccountingPrincipleLineItems_a37f3f74-d74f-4a6d-8791-00324a535843" xlink:to="loc_us-gaap_GoodwillAndIntangibleAssetsPolicyTextBlock_21d5b29c-3960-43d5-ab4a-dcf3557df2ef" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_ReverseRepurchaseAgreementsPolicyPolicyTextBlock_b2d6c5d1-0f0b-421b-8bb8-621f69101993" xlink:href="agnc-20220331.xsd#agnc_ReverseRepurchaseAgreementsPolicyPolicyTextBlock"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_NewAccountingPronouncementsOrChangeInAccountingPrincipleLineItems_a37f3f74-d74f-4a6d-8791-00324a535843" xlink:to="loc_agnc_ReverseRepurchaseAgreementsPolicyPolicyTextBlock_b2d6c5d1-0f0b-421b-8bb8-621f69101993" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_NewAccountingPronouncementsPolicyPolicyTextBlock_f59b2bcd-e577-48c0-8c25-99fb1da33dac" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_NewAccountingPronouncementsPolicyPolicyTextBlock"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_NewAccountingPronouncementsOrChangeInAccountingPrincipleLineItems_a37f3f74-d74f-4a6d-8791-00324a535843" xlink:to="loc_us-gaap_NewAccountingPronouncementsPolicyPolicyTextBlock_f59b2bcd-e577-48c0-8c25-99fb1da33dac" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_VariableInterestEntityDisclosureTextBlock_f81c5e7b-6fe7-41fd-9e54-76a0ab7d002b" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_VariableInterestEntityDisclosureTextBlock"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_NewAccountingPronouncementsOrChangeInAccountingPrincipleLineItems_a37f3f74-d74f-4a6d-8791-00324a535843" xlink:to="loc_us-gaap_VariableInterestEntityDisclosureTextBlock_f81c5e7b-6fe7-41fd-9e54-76a0ab7d002b" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationOptionAndIncentivePlansPolicy_db2af2e0-5777-43db-8990-86e99952d76b" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationOptionAndIncentivePlansPolicy"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_NewAccountingPronouncementsOrChangeInAccountingPrincipleLineItems_a37f3f74-d74f-4a6d-8791-00324a535843" xlink:to="loc_us-gaap_ShareBasedCompensationOptionAndIncentivePlansPolicy_db2af2e0-5777-43db-8990-86e99952d76b" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_UseOfEstimates_8fbbf634-a6b7-480c-a21d-75f667073caa" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_UseOfEstimates"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_NewAccountingPronouncementsOrChangeInAccountingPrincipleLineItems_a37f3f74-d74f-4a6d-8791-00324a535843" xlink:to="loc_us-gaap_UseOfEstimates_8fbbf634-a6b7-480c-a21d-75f667073caa" xlink:type="arc" order="7"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EarningsPerSharePolicyTextBlock_a421a044-8dd6-4b10-88ae-112a7b3d713b" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_EarningsPerSharePolicyTextBlock"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_NewAccountingPronouncementsOrChangeInAccountingPrincipleLineItems_a37f3f74-d74f-4a6d-8791-00324a535843" xlink:to="loc_us-gaap_EarningsPerSharePolicyTextBlock_a421a044-8dd6-4b10-88ae-112a7b3d713b" xlink:type="arc" order="8"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ComprehensiveIncomePolicyPolicyTextBlock_a75eb1a1-4335-4639-83a6-777befc65b9f" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ComprehensiveIncomePolicyPolicyTextBlock"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_NewAccountingPronouncementsOrChangeInAccountingPrincipleLineItems_a37f3f74-d74f-4a6d-8791-00324a535843" xlink:to="loc_us-gaap_ComprehensiveIncomePolicyPolicyTextBlock_a75eb1a1-4335-4639-83a6-777befc65b9f" xlink:type="arc" order="9"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CashAndCashEquivalentsPolicyTextBlock_c7043c18-b866-4608-9f07-e93eee45cfd7" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_CashAndCashEquivalentsPolicyTextBlock"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_NewAccountingPronouncementsOrChangeInAccountingPrincipleLineItems_a37f3f74-d74f-4a6d-8791-00324a535843" xlink:to="loc_us-gaap_CashAndCashEquivalentsPolicyTextBlock_c7043c18-b866-4608-9f07-e93eee45cfd7" xlink:type="arc" order="10"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_GoodwillDisclosureTextBlock_fb65b4f3-c959-4b0a-b3b8-f12e2278158a" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_GoodwillDisclosureTextBlock"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_NewAccountingPronouncementsOrChangeInAccountingPrincipleLineItems_a37f3f74-d74f-4a6d-8791-00324a535843" xlink:to="loc_us-gaap_GoodwillDisclosureTextBlock_fb65b4f3-c959-4b0a-b3b8-f12e2278158a" xlink:type="arc" order="11"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_NewAccountingPronouncementsOrChangeInAccountingPrincipleTable_0c6668f3-c24b-4140-bb7a-65b0afc0bff7" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_NewAccountingPronouncementsOrChangeInAccountingPrincipleTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_NewAccountingPronouncementsOrChangeInAccountingPrincipleLineItems_a37f3f74-d74f-4a6d-8791-00324a535843" xlink:to="loc_us-gaap_NewAccountingPronouncementsOrChangeInAccountingPrincipleTable_0c6668f3-c24b-4140-bb7a-65b0afc0bff7" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AdjustmentsForChangeInAccountingPrincipleAxis_05fba39d-00f7-4a97-9dd8-5930611e2a7e" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AdjustmentsForChangeInAccountingPrincipleAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_NewAccountingPronouncementsOrChangeInAccountingPrincipleTable_0c6668f3-c24b-4140-bb7a-65b0afc0bff7" xlink:to="loc_us-gaap_AdjustmentsForChangeInAccountingPrincipleAxis_05fba39d-00f7-4a97-9dd8-5930611e2a7e" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ChangeInAccountingPrincipleMember_05fba39d-00f7-4a97-9dd8-5930611e2a7e_default" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ChangeInAccountingPrincipleMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_AdjustmentsForChangeInAccountingPrincipleAxis_05fba39d-00f7-4a97-9dd8-5930611e2a7e" xlink:to="loc_us-gaap_ChangeInAccountingPrincipleMember_05fba39d-00f7-4a97-9dd8-5930611e2a7e_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ChangeInAccountingPrincipleMember_ab7a6a89-afd8-4ca3-9c11-e696399dbf5a" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ChangeInAccountingPrincipleMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_AdjustmentsForChangeInAccountingPrincipleAxis_05fba39d-00f7-4a97-9dd8-5930611e2a7e" xlink:to="loc_us-gaap_ChangeInAccountingPrincipleMember_ab7a6a89-afd8-4ca3-9c11-e696399dbf5a" xlink:type="arc" order="1"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.agnc.com/role/SummaryofSignificantAccountingPoliciesAccountingPoliciesPolicies" xlink:type="simple" xlink:href="agnc-20220331.xsd#SummaryofSignificantAccountingPoliciesAccountingPoliciesPolicies"/>
  <link:definitionLink xlink:role="http://www.agnc.com/role/SummaryofSignificantAccountingPoliciesAccountingPoliciesPolicies" xlink:type="extended" id="ib3b20cea43f7463eab46ec0601e7eab3_SummaryofSignificantAccountingPoliciesAccountingPoliciesPolicies">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_NewAccountingPronouncementsOrChangeInAccountingPrincipleLineItems_fc85549d-43be-416f-aca0-5dad664c287b" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_NewAccountingPronouncementsOrChangeInAccountingPrincipleLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationOptionAndIncentivePlansPolicy_0c2538f4-dcef-4fe9-b630-27fe3663bce1" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationOptionAndIncentivePlansPolicy"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_NewAccountingPronouncementsOrChangeInAccountingPrincipleLineItems_fc85549d-43be-416f-aca0-5dad664c287b" xlink:to="loc_us-gaap_ShareBasedCompensationOptionAndIncentivePlansPolicy_0c2538f4-dcef-4fe9-b630-27fe3663bce1" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DerivativesPolicyTextBlock_330fddcc-74cd-4ac4-a6d0-2557753a7c18" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DerivativesPolicyTextBlock"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_NewAccountingPronouncementsOrChangeInAccountingPrincipleLineItems_fc85549d-43be-416f-aca0-5dad664c287b" xlink:to="loc_us-gaap_DerivativesPolicyTextBlock_330fddcc-74cd-4ac4-a6d0-2557753a7c18" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_InvestmentPolicyTextBlock_eac54c2c-07f5-4e3b-88ee-56b52619eb9f" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_InvestmentPolicyTextBlock"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_NewAccountingPronouncementsOrChangeInAccountingPrincipleLineItems_fc85549d-43be-416f-aca0-5dad664c287b" xlink:to="loc_us-gaap_InvestmentPolicyTextBlock_eac54c2c-07f5-4e3b-88ee-56b52619eb9f" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_InterestIncomePolicyTextBlock_aa618bfa-4a6e-4a8e-a6cf-9170453c7e82" xlink:href="agnc-20220331.xsd#agnc_InterestIncomePolicyTextBlock"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_NewAccountingPronouncementsOrChangeInAccountingPrincipleLineItems_fc85549d-43be-416f-aca0-5dad664c287b" xlink:to="loc_agnc_InterestIncomePolicyTextBlock_aa618bfa-4a6e-4a8e-a6cf-9170453c7e82" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_ManagementAgreementTextBlock_39210385-2bb8-4890-911d-c1158f4fa227" xlink:href="agnc-20220331.xsd#agnc_ManagementAgreementTextBlock"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_NewAccountingPronouncementsOrChangeInAccountingPrincipleLineItems_fc85549d-43be-416f-aca0-5dad664c287b" xlink:to="loc_agnc_ManagementAgreementTextBlock_39210385-2bb8-4890-911d-c1158f4fa227" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_NewAccountingPronouncementsOrChangeInAccountingPrincipleTable_1be3b5b3-fff1-4946-b8fe-a5a68f285309" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_NewAccountingPronouncementsOrChangeInAccountingPrincipleTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_NewAccountingPronouncementsOrChangeInAccountingPrincipleLineItems_fc85549d-43be-416f-aca0-5dad664c287b" xlink:to="loc_us-gaap_NewAccountingPronouncementsOrChangeInAccountingPrincipleTable_1be3b5b3-fff1-4946-b8fe-a5a68f285309" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AdjustmentsForChangeInAccountingPrincipleAxis_6e23fb74-7312-4767-917a-cd1cf26ae94d" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AdjustmentsForChangeInAccountingPrincipleAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_NewAccountingPronouncementsOrChangeInAccountingPrincipleTable_1be3b5b3-fff1-4946-b8fe-a5a68f285309" xlink:to="loc_us-gaap_AdjustmentsForChangeInAccountingPrincipleAxis_6e23fb74-7312-4767-917a-cd1cf26ae94d" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ChangeInAccountingPrincipleMember_6e23fb74-7312-4767-917a-cd1cf26ae94d_default" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ChangeInAccountingPrincipleMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_AdjustmentsForChangeInAccountingPrincipleAxis_6e23fb74-7312-4767-917a-cd1cf26ae94d" xlink:to="loc_us-gaap_ChangeInAccountingPrincipleMember_6e23fb74-7312-4767-917a-cd1cf26ae94d_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ChangeInAccountingPrincipleMember_69bb09e1-0678-48aa-8f96-b631bd12d8e4" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ChangeInAccountingPrincipleMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_AdjustmentsForChangeInAccountingPrincipleAxis_6e23fb74-7312-4767-917a-cd1cf26ae94d" xlink:to="loc_us-gaap_ChangeInAccountingPrincipleMember_69bb09e1-0678-48aa-8f96-b631bd12d8e4" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_DiscontinuationOfElectionToAccountForInterestRateSwapsAsDesignatedCashFlowHedgesMember_49cc92ed-dff5-4419-996f-ed891beaeeb4" xlink:href="agnc-20220331.xsd#agnc_DiscontinuationOfElectionToAccountForInterestRateSwapsAsDesignatedCashFlowHedgesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ChangeInAccountingPrincipleMember_69bb09e1-0678-48aa-8f96-b631bd12d8e4" xlink:to="loc_agnc_DiscontinuationOfElectionToAccountForInterestRateSwapsAsDesignatedCashFlowHedgesMember_49cc92ed-dff5-4419-996f-ed891beaeeb4" xlink:type="arc" order="0"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.agnc.com/role/SummaryofSignificantAccountingPoliciesDetails" xlink:type="simple" xlink:href="agnc-20220331.xsd#SummaryofSignificantAccountingPoliciesDetails"/>
  <link:definitionLink xlink:role="http://www.agnc.com/role/SummaryofSignificantAccountingPoliciesDetails" xlink:type="extended" id="ia4d30a017dc140fb860f1e34d25b848a_SummaryofSignificantAccountingPoliciesDetails">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DerivativeLineItems_e02b447b-b94c-4c3d-a47e-96d8f2392f4f" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DerivativeLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_GainLossOnContractTermination_77446d9b-ff30-44d2-99fa-eb27e6cbe193" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_GainLossOnContractTermination"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DerivativeLineItems_e02b447b-b94c-4c3d-a47e-96d8f2392f4f" xlink:to="loc_us-gaap_GainLossOnContractTermination_77446d9b-ff30-44d2-99fa-eb27e6cbe193" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_RequiredAnnualDistributionOfTaxableNetIncome_21f6cdfd-b26a-48d4-877b-e3e0c5781da0" xlink:href="agnc-20220331.xsd#agnc_RequiredAnnualDistributionOfTaxableNetIncome"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DerivativeLineItems_e02b447b-b94c-4c3d-a47e-96d8f2392f4f" xlink:to="loc_agnc_RequiredAnnualDistributionOfTaxableNetIncome_21f6cdfd-b26a-48d4-877b-e3e0c5781da0" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IndefiniteLivedIntangibleAssetsWrittenOffRelatedToSaleOfBusinessUnit_af5ceeca-4252-49f7-86b9-0895b82d2c72" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_IndefiniteLivedIntangibleAssetsWrittenOffRelatedToSaleOfBusinessUnit"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DerivativeLineItems_e02b447b-b94c-4c3d-a47e-96d8f2392f4f" xlink:to="loc_us-gaap_IndefiniteLivedIntangibleAssetsWrittenOffRelatedToSaleOfBusinessUnit_af5ceeca-4252-49f7-86b9-0895b82d2c72" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DerivativeTable_34cc1fe8-64bc-4486-b2ad-69d61e9516d9" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DerivativeTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_DerivativeLineItems_e02b447b-b94c-4c3d-a47e-96d8f2392f4f" xlink:to="loc_us-gaap_DerivativeTable_34cc1fe8-64bc-4486-b2ad-69d61e9516d9" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeAxis_664d453b-5d30-4e97-a2c4-f7e2a43210e9" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_RangeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_DerivativeTable_34cc1fe8-64bc-4486-b2ad-69d61e9516d9" xlink:to="loc_srt_RangeAxis_664d453b-5d30-4e97-a2c4-f7e2a43210e9" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeMember_664d453b-5d30-4e97-a2c4-f7e2a43210e9_default" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_RangeMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_RangeAxis_664d453b-5d30-4e97-a2c4-f7e2a43210e9" xlink:to="loc_srt_RangeMember_664d453b-5d30-4e97-a2c4-f7e2a43210e9_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeMember_63fca936-ed6f-4215-9fbe-a961dd8d14d3" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_RangeMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_RangeAxis_664d453b-5d30-4e97-a2c4-f7e2a43210e9" xlink:to="loc_srt_RangeMember_63fca936-ed6f-4215-9fbe-a961dd8d14d3" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DerivativeInstrumentRiskAxis_ea5e58d6-b1a7-49a0-a1e3-38f0d57d9d88" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DerivativeInstrumentRiskAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_DerivativeTable_34cc1fe8-64bc-4486-b2ad-69d61e9516d9" xlink:to="loc_us-gaap_DerivativeInstrumentRiskAxis_ea5e58d6-b1a7-49a0-a1e3-38f0d57d9d88" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DerivativeContractTypeDomain_ea5e58d6-b1a7-49a0-a1e3-38f0d57d9d88_default" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DerivativeContractTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_DerivativeInstrumentRiskAxis_ea5e58d6-b1a7-49a0-a1e3-38f0d57d9d88" xlink:to="loc_us-gaap_DerivativeContractTypeDomain_ea5e58d6-b1a7-49a0-a1e3-38f0d57d9d88_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DerivativeContractTypeDomain_d7afa44a-c4b0-4214-b49f-00186b7b6f69" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DerivativeContractTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_DerivativeInstrumentRiskAxis_ea5e58d6-b1a7-49a0-a1e3-38f0d57d9d88" xlink:to="loc_us-gaap_DerivativeContractTypeDomain_d7afa44a-c4b0-4214-b49f-00186b7b6f69" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_InterestRateSwapMember_d75070d1-ec42-415f-bdca-435efcc7eecf" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_InterestRateSwapMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DerivativeContractTypeDomain_d7afa44a-c4b0-4214-b49f-00186b7b6f69" xlink:to="loc_us-gaap_InterestRateSwapMember_d75070d1-ec42-415f-bdca-435efcc7eecf" xlink:type="arc" order="0"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.agnc.com/role/SummaryofSignificantAccountingPoliciesGoodwillandIntangibleAssetsDetails" xlink:type="simple" xlink:href="agnc-20220331.xsd#SummaryofSignificantAccountingPoliciesGoodwillandIntangibleAssetsDetails"/>
  <link:definitionLink xlink:role="http://www.agnc.com/role/SummaryofSignificantAccountingPoliciesGoodwillandIntangibleAssetsDetails" xlink:type="extended" id="ief05fad275744e57a5850352f77a514f_SummaryofSignificantAccountingPoliciesGoodwillandIntangibleAssetsDetails">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FiniteLivedIntangibleAssetsLineItems_4ee7a9a8-5f59-4936-9f73-463a8f28c017" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FiniteLivedIntangibleAssetsLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_Goodwill_c1d69c7b-ff7d-4e51-8db3-39ac8bfe2d02" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_Goodwill"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FiniteLivedIntangibleAssetsLineItems_4ee7a9a8-5f59-4936-9f73-463a8f28c017" xlink:to="loc_us-gaap_Goodwill_c1d69c7b-ff7d-4e51-8db3-39ac8bfe2d02" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IntangibleAssetsNetExcludingGoodwill_7a55af93-7900-463a-b32c-f543d439e1ba" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_IntangibleAssetsNetExcludingGoodwill"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FiniteLivedIntangibleAssetsLineItems_4ee7a9a8-5f59-4936-9f73-463a8f28c017" xlink:to="loc_us-gaap_IntangibleAssetsNetExcludingGoodwill_7a55af93-7900-463a-b32c-f543d439e1ba" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfFiniteLivedIntangibleAssetsTable_159df1ae-73f9-4294-83df-2da2b5dfd72e" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ScheduleOfFiniteLivedIntangibleAssetsTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_FiniteLivedIntangibleAssetsLineItems_4ee7a9a8-5f59-4936-9f73-463a8f28c017" xlink:to="loc_us-gaap_ScheduleOfFiniteLivedIntangibleAssetsTable_159df1ae-73f9-4294-83df-2da2b5dfd72e" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FiniteLivedIntangibleAssetsByMajorClassAxis_4e51c09e-d518-492a-bf4b-0013cec7bd9b" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FiniteLivedIntangibleAssetsByMajorClassAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfFiniteLivedIntangibleAssetsTable_159df1ae-73f9-4294-83df-2da2b5dfd72e" xlink:to="loc_us-gaap_FiniteLivedIntangibleAssetsByMajorClassAxis_4e51c09e-d518-492a-bf4b-0013cec7bd9b" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain_4e51c09e-d518-492a-bf4b-0013cec7bd9b_default" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_FiniteLivedIntangibleAssetsByMajorClassAxis_4e51c09e-d518-492a-bf4b-0013cec7bd9b" xlink:to="loc_us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain_4e51c09e-d518-492a-bf4b-0013cec7bd9b_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain_6443e595-68da-4f06-8a14-f0e4355948ea" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_FiniteLivedIntangibleAssetsByMajorClassAxis_4e51c09e-d518-492a-bf4b-0013cec7bd9b" xlink:to="loc_us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain_6443e595-68da-4f06-8a14-f0e4355948ea" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ConsolidationItemsAxis_628c5be1-4f39-4244-8876-ab55c053abbf" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_ConsolidationItemsAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfFiniteLivedIntangibleAssetsTable_159df1ae-73f9-4294-83df-2da2b5dfd72e" xlink:to="loc_srt_ConsolidationItemsAxis_628c5be1-4f39-4244-8876-ab55c053abbf" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ConsolidationItemsDomain_628c5be1-4f39-4244-8876-ab55c053abbf_default" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_ConsolidationItemsDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_ConsolidationItemsAxis_628c5be1-4f39-4244-8876-ab55c053abbf" xlink:to="loc_srt_ConsolidationItemsDomain_628c5be1-4f39-4244-8876-ab55c053abbf_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ConsolidationItemsDomain_14ea1b18-4d20-4ebb-b535-1765bf31d294" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_ConsolidationItemsDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_ConsolidationItemsAxis_628c5be1-4f39-4244-8876-ab55c053abbf" xlink:to="loc_srt_ConsolidationItemsDomain_14ea1b18-4d20-4ebb-b535-1765bf31d294" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StatementBusinessSegmentsAxis_e31e01ae-ae0a-41b5-9793-643bc5e86bc4" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_StatementBusinessSegmentsAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfFiniteLivedIntangibleAssetsTable_159df1ae-73f9-4294-83df-2da2b5dfd72e" xlink:to="loc_us-gaap_StatementBusinessSegmentsAxis_e31e01ae-ae0a-41b5-9793-643bc5e86bc4" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SegmentDomain_e31e01ae-ae0a-41b5-9793-643bc5e86bc4_default" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_SegmentDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_StatementBusinessSegmentsAxis_e31e01ae-ae0a-41b5-9793-643bc5e86bc4" xlink:to="loc_us-gaap_SegmentDomain_e31e01ae-ae0a-41b5-9793-643bc5e86bc4_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SegmentDomain_80a00479-a92c-461e-a594-553e5f2fb2cb" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_SegmentDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_StatementBusinessSegmentsAxis_e31e01ae-ae0a-41b5-9793-643bc5e86bc4" xlink:to="loc_us-gaap_SegmentDomain_80a00479-a92c-461e-a594-553e5f2fb2cb" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeAxis_00dca215-2394-4d88-9460-296a0680b275" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_RangeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfFiniteLivedIntangibleAssetsTable_159df1ae-73f9-4294-83df-2da2b5dfd72e" xlink:to="loc_srt_RangeAxis_00dca215-2394-4d88-9460-296a0680b275" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeMember_00dca215-2394-4d88-9460-296a0680b275_default" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_RangeMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_RangeAxis_00dca215-2394-4d88-9460-296a0680b275" xlink:to="loc_srt_RangeMember_00dca215-2394-4d88-9460-296a0680b275_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeMember_979c1212-4bad-46e6-ac69-0cc95d89cef0" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_RangeMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_RangeAxis_00dca215-2394-4d88-9460-296a0680b275" xlink:to="loc_srt_RangeMember_979c1212-4bad-46e6-ac69-0cc95d89cef0" xlink:type="arc" order="1"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.agnc.com/role/SummaryofSignificantAccountingPoliciesVariableInterestEntitiesDetails" xlink:type="simple" xlink:href="agnc-20220331.xsd#SummaryofSignificantAccountingPoliciesVariableInterestEntitiesDetails"/>
  <link:definitionLink xlink:role="http://www.agnc.com/role/SummaryofSignificantAccountingPoliciesVariableInterestEntitiesDetails" xlink:type="extended" id="ia7f891335692429b9eca16948c4a4fdf_SummaryofSignificantAccountingPoliciesVariableInterestEntitiesDetails">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_VariableInterestEntityLineItems_e6dbd3c7-8e15-4fd6-b0d7-1cb23ea3bfd3" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_VariableInterestEntityLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherLongTermDebt_4df5f2ac-ef48-4708-9768-a1253a539e42" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_OtherLongTermDebt"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_VariableInterestEntityLineItems_e6dbd3c7-8e15-4fd6-b0d7-1cb23ea3bfd3" xlink:to="loc_us-gaap_OtherLongTermDebt_4df5f2ac-ef48-4708-9768-a1253a539e42" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentDescriptionOfVariableRateBasis_30ac6a82-fe9c-4866-bc99-23597d101e61" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DebtInstrumentDescriptionOfVariableRateBasis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_VariableInterestEntityLineItems_e6dbd3c7-8e15-4fd6-b0d7-1cb23ea3bfd3" xlink:to="loc_us-gaap_DebtInstrumentDescriptionOfVariableRateBasis_30ac6a82-fe9c-4866-bc99-23597d101e61" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_SpreadOverLibor_af41cf82-72e0-47a6-8e01-4f3ab8727091" xlink:href="agnc-20220331.xsd#agnc_SpreadOverLibor"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_VariableInterestEntityLineItems_e6dbd3c7-8e15-4fd6-b0d7-1cb23ea3bfd3" xlink:to="loc_agnc_SpreadOverLibor_af41cf82-72e0-47a6-8e01-4f3ab8727091" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_WeightedAverageLifeOtherDebt_64c284ff-59a6-4129-b1ac-6746a18a2e9a" xlink:href="agnc-20220331.xsd#agnc_WeightedAverageLifeOtherDebt"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_VariableInterestEntityLineItems_e6dbd3c7-8e15-4fd6-b0d7-1cb23ea3bfd3" xlink:to="loc_agnc_WeightedAverageLifeOtherDebt_64c284ff-59a6-4129-b1ac-6746a18a2e9a" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfVariableInterestEntitiesTable_6e783c18-133a-477e-a08a-288b19ea1e03" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ScheduleOfVariableInterestEntitiesTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_VariableInterestEntityLineItems_e6dbd3c7-8e15-4fd6-b0d7-1cb23ea3bfd3" xlink:to="loc_us-gaap_ScheduleOfVariableInterestEntitiesTable_6e783c18-133a-477e-a08a-288b19ea1e03" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentAxis_5b1c0d65-3bff-4da3-bc92-469b951b38a9" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DebtInstrumentAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfVariableInterestEntitiesTable_6e783c18-133a-477e-a08a-288b19ea1e03" xlink:to="loc_us-gaap_DebtInstrumentAxis_5b1c0d65-3bff-4da3-bc92-469b951b38a9" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentNameDomain_5b1c0d65-3bff-4da3-bc92-469b951b38a9_default" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DebtInstrumentNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_DebtInstrumentAxis_5b1c0d65-3bff-4da3-bc92-469b951b38a9" xlink:to="loc_us-gaap_DebtInstrumentNameDomain_5b1c0d65-3bff-4da3-bc92-469b951b38a9_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentNameDomain_b9f78e93-319f-4436-bbd2-79b59b8dde64" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DebtInstrumentNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_DebtInstrumentAxis_5b1c0d65-3bff-4da3-bc92-469b951b38a9" xlink:to="loc_us-gaap_DebtInstrumentNameDomain_b9f78e93-319f-4436-bbd2-79b59b8dde64" xlink:type="arc" order="1"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.agnc.com/role/InvestmentSecuritiesNarrativeDetails" xlink:type="simple" xlink:href="agnc-20220331.xsd#InvestmentSecuritiesNarrativeDetails"/>
  <link:definitionLink xlink:role="http://www.agnc.com/role/InvestmentSecuritiesNarrativeDetails" xlink:type="extended" id="i9ef6688efc314384ba5c721c861141ae_InvestmentSecuritiesNarrativeDetails">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems_b26ede8c-30b1-4f53-a829-381034dc4f9e" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_MortgageBackedSecuritiesAvailableForSaleFairValueDisclosure_2038cd3a-cb1d-465e-b6fe-91228f36a997" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_MortgageBackedSecuritiesAvailableForSaleFairValueDisclosure"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems_b26ede8c-30b1-4f53-a829-381034dc4f9e" xlink:to="loc_us-gaap_MortgageBackedSecuritiesAvailableForSaleFairValueDisclosure_2038cd3a-cb1d-465e-b6fe-91228f36a997" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DerivativeFairValueOfDerivativeAsset_449be103-cf03-4628-b85a-391652ed9f8d" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DerivativeFairValueOfDerivativeAsset"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems_b26ede8c-30b1-4f53-a829-381034dc4f9e" xlink:to="loc_us-gaap_DerivativeFairValueOfDerivativeAsset_449be103-cf03-4628-b85a-391652ed9f8d" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DerivativeFairValueOfDerivativeNet_6d0871e9-e921-4ca0-aefc-b2ec54e3aacb" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DerivativeFairValueOfDerivativeNet"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems_b26ede8c-30b1-4f53-a829-381034dc4f9e" xlink:to="loc_us-gaap_DerivativeFairValueOfDerivativeNet_6d0871e9-e921-4ca0-aefc-b2ec54e3aacb" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentUnamortizedDiscountPremiumNet_6aae36b9-20ff-4432-bbf6-09607bf35e67" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DebtInstrumentUnamortizedDiscountPremiumNet"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems_b26ede8c-30b1-4f53-a829-381034dc4f9e" xlink:to="loc_us-gaap_DebtInstrumentUnamortizedDiscountPremiumNet_6aae36b9-20ff-4432-bbf6-09607bf35e67" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_FuturePrepaymentRateAssumptionOfInvestmentPortfolio_d1497b43-76c2-41c1-9229-a1da91deecca" xlink:href="agnc-20220331.xsd#agnc_FuturePrepaymentRateAssumptionOfInvestmentPortfolio"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems_b26ede8c-30b1-4f53-a829-381034dc4f9e" xlink:to="loc_agnc_FuturePrepaymentRateAssumptionOfInvestmentPortfolio_d1497b43-76c2-41c1-9229-a1da91deecca" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_WeightedAverageCouponRate_3775522a-1004-40d8-91a5-779a93bed643" xlink:href="agnc-20220331.xsd#agnc_WeightedAverageCouponRate"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems_b26ede8c-30b1-4f53-a829-381034dc4f9e" xlink:to="loc_agnc_WeightedAverageCouponRate_3775522a-1004-40d8-91a5-779a93bed643" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_UnderlyingCollateralCoupon_d878b37e-80d6-42ef-aeb3-b08c86a9d478" xlink:href="agnc-20220331.xsd#agnc_UnderlyingCollateralCoupon"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems_b26ede8c-30b1-4f53-a829-381034dc4f9e" xlink:to="loc_agnc_UnderlyingCollateralCoupon_d878b37e-80d6-42ef-aeb3-b08c86a9d478" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_SecuritiesRemeasuredatFairValueThroughEarningsDebtSecurities_041471c0-bf3b-46b1-acd5-fe9ec9b7b401" xlink:href="agnc-20220331.xsd#agnc_SecuritiesRemeasuredatFairValueThroughEarningsDebtSecurities"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems_b26ede8c-30b1-4f53-a829-381034dc4f9e" xlink:to="loc_agnc_SecuritiesRemeasuredatFairValueThroughEarningsDebtSecurities_041471c0-bf3b-46b1-acd5-fe9ec9b7b401" xlink:type="arc" order="7"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SecuritiesHeldAsCollateralAtFairValue_b9946e64-2404-4e30-8045-c978b3099279" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_SecuritiesHeldAsCollateralAtFairValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems_b26ede8c-30b1-4f53-a829-381034dc4f9e" xlink:to="loc_us-gaap_SecuritiesHeldAsCollateralAtFairValue_b9946e64-2404-4e30-8045-c978b3099279" xlink:type="arc" order="8"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherLongTermDebt_c92ef626-2bde-417e-a98b-ad602d29df28" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_OtherLongTermDebt"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems_b26ede8c-30b1-4f53-a829-381034dc4f9e" xlink:to="loc_us-gaap_OtherLongTermDebt_c92ef626-2bde-417e-a98b-ad602d29df28" xlink:type="arc" order="9"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentFaceAmount_e8c7d0e2-6a04-445d-bb82-1d5be8c9a1e9" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DebtInstrumentFaceAmount"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems_b26ede8c-30b1-4f53-a829-381034dc4f9e" xlink:to="loc_us-gaap_DebtInstrumentFaceAmount_e8c7d0e2-6a04-445d-bb82-1d5be8c9a1e9" xlink:type="arc" order="10"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_FairValueOfCmoSecuritiesDirectlyHeld_b4865544-db9f-4af1-bebc-65fcd2eb2edd" xlink:href="agnc-20220331.xsd#agnc_FairValueOfCmoSecuritiesDirectlyHeld"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems_b26ede8c-30b1-4f53-a829-381034dc4f9e" xlink:to="loc_agnc_FairValueOfCmoSecuritiesDirectlyHeld_b4865544-db9f-4af1-bebc-65fcd2eb2edd" xlink:type="arc" order="11"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_SecuritizedCmoSecurities_bf840709-e560-4738-bd86-1f57caecbef7" xlink:href="agnc-20220331.xsd#agnc_SecuritizedCmoSecurities"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems_b26ede8c-30b1-4f53-a829-381034dc4f9e" xlink:to="loc_agnc_SecuritizedCmoSecurities_bf840709-e560-4738-bd86-1f57caecbef7" xlink:type="arc" order="12"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_CmoAndInterestOnlyPricincipalOnlySecuritiesMaximumLossExposure_234a2e3b-cd0e-4d6c-972f-ee5493b71320" xlink:href="agnc-20220331.xsd#agnc_CmoAndInterestOnlyPricincipalOnlySecuritiesMaximumLossExposure"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems_b26ede8c-30b1-4f53-a829-381034dc4f9e" xlink:to="loc_agnc_CmoAndInterestOnlyPricincipalOnlySecuritiesMaximumLossExposure_234a2e3b-cd0e-4d6c-972f-ee5493b71320" xlink:type="arc" order="13"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AvailableForSaleSecuritiesDebtSecurities_2e2c2d0e-8159-427b-be53-7b41544a834f" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AvailableForSaleSecuritiesDebtSecurities"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems_b26ede8c-30b1-4f53-a829-381034dc4f9e" xlink:to="loc_us-gaap_AvailableForSaleSecuritiesDebtSecurities_2e2c2d0e-8159-427b-be53-7b41544a834f" xlink:type="arc" order="14"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfAvailableForSaleSecuritiesTable_067cfbd0-b1d2-4f9e-8cf7-be85ea5640fa" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ScheduleOfAvailableForSaleSecuritiesTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems_b26ede8c-30b1-4f53-a829-381034dc4f9e" xlink:to="loc_us-gaap_ScheduleOfAvailableForSaleSecuritiesTable_067cfbd0-b1d2-4f9e-8cf7-be85ea5640fa" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FinancialInstrumentAxis_19218ac3-b0aa-4a13-89fc-6ca7e6a6a763" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FinancialInstrumentAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfAvailableForSaleSecuritiesTable_067cfbd0-b1d2-4f9e-8cf7-be85ea5640fa" xlink:to="loc_us-gaap_FinancialInstrumentAxis_19218ac3-b0aa-4a13-89fc-6ca7e6a6a763" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_19218ac3-b0aa-4a13-89fc-6ca7e6a6a763_default" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_FinancialInstrumentAxis_19218ac3-b0aa-4a13-89fc-6ca7e6a6a763" xlink:to="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_19218ac3-b0aa-4a13-89fc-6ca7e6a6a763_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_281203b3-ad20-4931-8e44-5c6154a673e6" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_FinancialInstrumentAxis_19218ac3-b0aa-4a13-89fc-6ca7e6a6a763" xlink:to="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_281203b3-ad20-4931-8e44-5c6154a673e6" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_CreditRiskTransferSecuritiesMember_573904ec-a3e4-425e-b121-d9c370c136cf" xlink:href="agnc-20220331.xsd#agnc_CreditRiskTransferSecuritiesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_281203b3-ad20-4931-8e44-5c6154a673e6" xlink:to="loc_agnc_CreditRiskTransferSecuritiesMember_573904ec-a3e4-425e-b121-d9c370c136cf" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeAxis_3ea460be-00e2-4ec9-b04e-fe81b0a3e1a3" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_RangeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfAvailableForSaleSecuritiesTable_067cfbd0-b1d2-4f9e-8cf7-be85ea5640fa" xlink:to="loc_srt_RangeAxis_3ea460be-00e2-4ec9-b04e-fe81b0a3e1a3" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeMember_3ea460be-00e2-4ec9-b04e-fe81b0a3e1a3_default" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_RangeMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_RangeAxis_3ea460be-00e2-4ec9-b04e-fe81b0a3e1a3" xlink:to="loc_srt_RangeMember_3ea460be-00e2-4ec9-b04e-fe81b0a3e1a3_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeMember_dcfa8db0-ef7b-43cd-b6b2-9b494cd17c9c" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_RangeMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_RangeAxis_3ea460be-00e2-4ec9-b04e-fe81b0a3e1a3" xlink:to="loc_srt_RangeMember_dcfa8db0-ef7b-43cd-b6b2-9b494cd17c9c" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_MinimumMember_662bbd7b-6674-4068-9708-195c4cf4df0b" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_MinimumMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RangeMember_dcfa8db0-ef7b-43cd-b6b2-9b494cd17c9c" xlink:to="loc_srt_MinimumMember_662bbd7b-6674-4068-9708-195c4cf4df0b" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_MaximumMember_36605d29-0665-422e-9029-5bb1bcff8cba" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_MaximumMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RangeMember_dcfa8db0-ef7b-43cd-b6b2-9b494cd17c9c" xlink:to="loc_srt_MaximumMember_36605d29-0665-422e-9029-5bb1bcff8cba" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DerivativeInstrumentRiskAxis_0cd13380-a943-4f63-9e42-21b4bc1b5b50" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DerivativeInstrumentRiskAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfAvailableForSaleSecuritiesTable_067cfbd0-b1d2-4f9e-8cf7-be85ea5640fa" xlink:to="loc_us-gaap_DerivativeInstrumentRiskAxis_0cd13380-a943-4f63-9e42-21b4bc1b5b50" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DerivativeContractTypeDomain_0cd13380-a943-4f63-9e42-21b4bc1b5b50_default" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DerivativeContractTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_DerivativeInstrumentRiskAxis_0cd13380-a943-4f63-9e42-21b4bc1b5b50" xlink:to="loc_us-gaap_DerivativeContractTypeDomain_0cd13380-a943-4f63-9e42-21b4bc1b5b50_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DerivativeContractTypeDomain_7750698e-3dbb-421c-9593-f3e84c0ee85d" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DerivativeContractTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_DerivativeInstrumentRiskAxis_0cd13380-a943-4f63-9e42-21b4bc1b5b50" xlink:to="loc_us-gaap_DerivativeContractTypeDomain_7750698e-3dbb-421c-9593-f3e84c0ee85d" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_TbaSecuritiesFifteenYearAndThirtyYearSecuritiesMember_865a30bb-f409-436e-a4e7-4cb074b8c2ea" xlink:href="agnc-20220331.xsd#agnc_TbaSecuritiesFifteenYearAndThirtyYearSecuritiesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DerivativeContractTypeDomain_7750698e-3dbb-421c-9593-f3e84c0ee85d" xlink:to="loc_agnc_TbaSecuritiesFifteenYearAndThirtyYearSecuritiesMember_865a30bb-f409-436e-a4e7-4cb074b8c2ea" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_ForwardSettlingNonAgencySecuritiesMember_027d0b7b-5c0a-44db-9fb8-9a808d85e812" xlink:href="agnc-20220331.xsd#agnc_ForwardSettlingNonAgencySecuritiesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DerivativeContractTypeDomain_7750698e-3dbb-421c-9593-f3e84c0ee85d" xlink:to="loc_agnc_ForwardSettlingNonAgencySecuritiesMember_027d0b7b-5c0a-44db-9fb8-9a808d85e812" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncomeStatementLocationAxis_0a227875-3a5a-4c91-9ffc-543227ad705e" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_IncomeStatementLocationAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfAvailableForSaleSecuritiesTable_067cfbd0-b1d2-4f9e-8cf7-be85ea5640fa" xlink:to="loc_us-gaap_IncomeStatementLocationAxis_0a227875-3a5a-4c91-9ffc-543227ad705e" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncomeStatementLocationDomain_0a227875-3a5a-4c91-9ffc-543227ad705e_default" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_IncomeStatementLocationDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_IncomeStatementLocationAxis_0a227875-3a5a-4c91-9ffc-543227ad705e" xlink:to="loc_us-gaap_IncomeStatementLocationDomain_0a227875-3a5a-4c91-9ffc-543227ad705e_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncomeStatementLocationDomain_356135ff-4fa9-47df-8f72-433a508f9d53" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_IncomeStatementLocationDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_IncomeStatementLocationAxis_0a227875-3a5a-4c91-9ffc-543227ad705e" xlink:to="loc_us-gaap_IncomeStatementLocationDomain_356135ff-4fa9-47df-8f72-433a508f9d53" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_InterestOnlyAndPrincipalOnlyStripMember_7c6abe79-134a-483d-b6c2-457a9203de1a" xlink:href="agnc-20220331.xsd#agnc_InterestOnlyAndPrincipalOnlyStripMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncomeStatementLocationDomain_356135ff-4fa9-47df-8f72-433a508f9d53" xlink:to="loc_agnc_InterestOnlyAndPrincipalOnlyStripMember_7c6abe79-134a-483d-b6c2-457a9203de1a" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_InvestmentTypeAxis_b099407d-5c50-40ee-93bb-13c655342f4d" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_InvestmentTypeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfAvailableForSaleSecuritiesTable_067cfbd0-b1d2-4f9e-8cf7-be85ea5640fa" xlink:to="loc_us-gaap_InvestmentTypeAxis_b099407d-5c50-40ee-93bb-13c655342f4d" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_InvestmentTypeCategorizationMember_b099407d-5c50-40ee-93bb-13c655342f4d_default" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_InvestmentTypeCategorizationMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_InvestmentTypeAxis_b099407d-5c50-40ee-93bb-13c655342f4d" xlink:to="loc_us-gaap_InvestmentTypeCategorizationMember_b099407d-5c50-40ee-93bb-13c655342f4d_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_InvestmentTypeCategorizationMember_ae5f1631-4ff0-4aab-b122-ec918ad33cac" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_InvestmentTypeCategorizationMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_InvestmentTypeAxis_b099407d-5c50-40ee-93bb-13c655342f4d" xlink:to="loc_us-gaap_InvestmentTypeCategorizationMember_ae5f1631-4ff0-4aab-b122-ec918ad33cac" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AgencySecuritiesMember_240a9059-5a04-4eb8-a0f1-a3a1a5398d8a" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AgencySecuritiesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_InvestmentTypeCategorizationMember_ae5f1631-4ff0-4aab-b122-ec918ad33cac" xlink:to="loc_us-gaap_AgencySecuritiesMember_240a9059-5a04-4eb8-a0f1-a3a1a5398d8a" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_MortgageBackedSecuritiesIssuedByPrivateEnterprisesMember_ea82298e-4b84-4d12-aa25-f79a8cb8579a" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_MortgageBackedSecuritiesIssuedByPrivateEnterprisesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_InvestmentTypeCategorizationMember_ae5f1631-4ff0-4aab-b122-ec918ad33cac" xlink:to="loc_us-gaap_MortgageBackedSecuritiesIssuedByPrivateEnterprisesMember_ea82298e-4b84-4d12-aa25-f79a8cb8579a" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_CreditRiskTransferSecuritiesMember_7d1e9e7e-c7c0-4aeb-91ad-21ff4c88a3ad" xlink:href="agnc-20220331.xsd#agnc_CreditRiskTransferSecuritiesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_InvestmentTypeCategorizationMember_ae5f1631-4ff0-4aab-b122-ec918ad33cac" xlink:to="loc_agnc_CreditRiskTransferSecuritiesMember_7d1e9e7e-c7c0-4aeb-91ad-21ff4c88a3ad" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CommercialMortgageBackedSecuritiesMember_e8ed59dd-3187-4ca9-a5f8-bc3b45a571da" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_CommercialMortgageBackedSecuritiesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_InvestmentTypeCategorizationMember_ae5f1631-4ff0-4aab-b122-ec918ad33cac" xlink:to="loc_us-gaap_CommercialMortgageBackedSecuritiesMember_e8ed59dd-3187-4ca9-a5f8-bc3b45a571da" xlink:type="arc" order="3"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.agnc.com/role/InvestmentSecuritiesInvestmentSecuritiesSummaryofInvestmentinAgencySecurityDetails" xlink:type="simple" xlink:href="agnc-20220331.xsd#InvestmentSecuritiesInvestmentSecuritiesSummaryofInvestmentinAgencySecurityDetails"/>
  <link:definitionLink xlink:role="http://www.agnc.com/role/InvestmentSecuritiesInvestmentSecuritiesSummaryofInvestmentinAgencySecurityDetails" xlink:type="extended" id="ib12d2404fb844121b71f4e0efa24a0e2_InvestmentSecuritiesInvestmentSecuritiesSummaryofInvestmentinAgencySecurityDetails">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfTradingSecuritiesAndOtherTradingAssetsLineItems_dd328c8d-a02c-49c2-ba31-c0c17d26142e" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ScheduleOfTradingSecuritiesAndOtherTradingAssetsLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_DebtSecuritiesTradingandAvailableforsaleAmortizedCostBasis_b175cc3a-e371-48ae-b6ce-24700e7baae5" xlink:href="agnc-20220331.xsd#agnc_DebtSecuritiesTradingandAvailableforsaleAmortizedCostBasis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ScheduleOfTradingSecuritiesAndOtherTradingAssetsLineItems_dd328c8d-a02c-49c2-ba31-c0c17d26142e" xlink:to="loc_agnc_DebtSecuritiesTradingandAvailableforsaleAmortizedCostBasis_b175cc3a-e371-48ae-b6ce-24700e7baae5" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtSecuritiesTradingAndAvailableForSale_1b42c560-0f93-405b-a02a-cb01372374dd" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DebtSecuritiesTradingAndAvailableForSale"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ScheduleOfTradingSecuritiesAndOtherTradingAssetsLineItems_dd328c8d-a02c-49c2-ba31-c0c17d26142e" xlink:to="loc_us-gaap_DebtSecuritiesTradingAndAvailableForSale_1b42c560-0f93-405b-a02a-cb01372374dd" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_TotalAgencySecurities_227b3be5-ff68-441b-8d63-8a9cffb1bbbf" xlink:href="agnc-20220331.xsd#agnc_TotalAgencySecurities"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ScheduleOfTradingSecuritiesAndOtherTradingAssetsLineItems_dd328c8d-a02c-49c2-ba31-c0c17d26142e" xlink:to="loc_agnc_TotalAgencySecurities_227b3be5-ff68-441b-8d63-8a9cffb1bbbf" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfTradingSecuritiesAndOtherTradingAssetsTable_e186e1da-0c84-4735-aa99-a25e0b4da721" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ScheduleOfTradingSecuritiesAndOtherTradingAssetsTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_ScheduleOfTradingSecuritiesAndOtherTradingAssetsLineItems_dd328c8d-a02c-49c2-ba31-c0c17d26142e" xlink:to="loc_us-gaap_ScheduleOfTradingSecuritiesAndOtherTradingAssetsTable_e186e1da-0c84-4735-aa99-a25e0b4da721" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FinancialInstrumentAxis_7b49e3ab-6058-4c33-a277-083f4430c354" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FinancialInstrumentAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfTradingSecuritiesAndOtherTradingAssetsTable_e186e1da-0c84-4735-aa99-a25e0b4da721" xlink:to="loc_us-gaap_FinancialInstrumentAxis_7b49e3ab-6058-4c33-a277-083f4430c354" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_7b49e3ab-6058-4c33-a277-083f4430c354_default" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_FinancialInstrumentAxis_7b49e3ab-6058-4c33-a277-083f4430c354" xlink:to="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_7b49e3ab-6058-4c33-a277-083f4430c354_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_d65e10c9-5b38-4e02-96a0-c610f03d98c8" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_FinancialInstrumentAxis_7b49e3ab-6058-4c33-a277-083f4430c354" xlink:to="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_d65e10c9-5b38-4e02-96a0-c610f03d98c8" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FixedIncomeSecuritiesMember_ab2c4717-69b6-4ead-a684-baaffd87afd9" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FixedIncomeSecuritiesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_d65e10c9-5b38-4e02-96a0-c610f03d98c8" xlink:to="loc_us-gaap_FixedIncomeSecuritiesMember_ab2c4717-69b6-4ead-a684-baaffd87afd9" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_AdjustableRateMember_0c3a8576-a7fe-4245-8315-608a78bbbdd2" xlink:href="agnc-20220331.xsd#agnc_AdjustableRateMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_d65e10c9-5b38-4e02-96a0-c610f03d98c8" xlink:to="loc_agnc_AdjustableRateMember_0c3a8576-a7fe-4245-8315-608a78bbbdd2" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CollateralizedMortgageObligationsMember_512ee2cf-cf1b-41ef-9ce3-1647b5853a62" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_CollateralizedMortgageObligationsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_d65e10c9-5b38-4e02-96a0-c610f03d98c8" xlink:to="loc_us-gaap_CollateralizedMortgageObligationsMember_512ee2cf-cf1b-41ef-9ce3-1647b5853a62" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_MultifamilyMember_c3a569b4-5903-46a8-a62d-bab7e1175215" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_MultifamilyMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_d65e10c9-5b38-4e02-96a0-c610f03d98c8" xlink:to="loc_srt_MultifamilyMember_c3a569b4-5903-46a8-a62d-bab7e1175215" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_InterestOnlyAndPrincipalOnlyStripMember_991d47ed-d272-4777-b0a2-ba5ba60de74e" xlink:href="agnc-20220331.xsd#agnc_InterestOnlyAndPrincipalOnlyStripMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_d65e10c9-5b38-4e02-96a0-c610f03d98c8" xlink:to="loc_agnc_InterestOnlyAndPrincipalOnlyStripMember_991d47ed-d272-4777-b0a2-ba5ba60de74e" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AgencySecuritiesMember_f9a9bfc5-77a4-46fa-8333-f750c1d54875" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AgencySecuritiesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_d65e10c9-5b38-4e02-96a0-c610f03d98c8" xlink:to="loc_us-gaap_AgencySecuritiesMember_f9a9bfc5-77a4-46fa-8333-f750c1d54875" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_InvestmentTypeAxis_1ae8d2de-9c3c-4293-92be-c9b454b9098b" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_InvestmentTypeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfTradingSecuritiesAndOtherTradingAssetsTable_e186e1da-0c84-4735-aa99-a25e0b4da721" xlink:to="loc_us-gaap_InvestmentTypeAxis_1ae8d2de-9c3c-4293-92be-c9b454b9098b" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_InvestmentTypeCategorizationMember_1ae8d2de-9c3c-4293-92be-c9b454b9098b_default" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_InvestmentTypeCategorizationMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_InvestmentTypeAxis_1ae8d2de-9c3c-4293-92be-c9b454b9098b" xlink:to="loc_us-gaap_InvestmentTypeCategorizationMember_1ae8d2de-9c3c-4293-92be-c9b454b9098b_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_InvestmentTypeCategorizationMember_25f43f1c-f731-4573-b22f-e4fd99beacfd" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_InvestmentTypeCategorizationMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_InvestmentTypeAxis_1ae8d2de-9c3c-4293-92be-c9b454b9098b" xlink:to="loc_us-gaap_InvestmentTypeCategorizationMember_25f43f1c-f731-4573-b22f-e4fd99beacfd" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AgencySecuritiesMember_451b1575-0b5a-45c1-8722-96df0705418a" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AgencySecuritiesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_InvestmentTypeCategorizationMember_25f43f1c-f731-4573-b22f-e4fd99beacfd" xlink:to="loc_us-gaap_AgencySecuritiesMember_451b1575-0b5a-45c1-8722-96df0705418a" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_MortgageBackedSecuritiesIssuedByPrivateEnterprisesMember_e8a83933-1d6b-4549-84e8-ead95fea73b2" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_MortgageBackedSecuritiesIssuedByPrivateEnterprisesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_InvestmentTypeCategorizationMember_25f43f1c-f731-4573-b22f-e4fd99beacfd" xlink:to="loc_us-gaap_MortgageBackedSecuritiesIssuedByPrivateEnterprisesMember_e8a83933-1d6b-4549-84e8-ead95fea73b2" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CommercialMortgageBackedSecuritiesMember_89f3fb02-2442-4362-9f49-5a80c3d280bd" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_CommercialMortgageBackedSecuritiesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_InvestmentTypeCategorizationMember_25f43f1c-f731-4573-b22f-e4fd99beacfd" xlink:to="loc_us-gaap_CommercialMortgageBackedSecuritiesMember_89f3fb02-2442-4362-9f49-5a80c3d280bd" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_CreditRiskTransferSecuritiesMember_4255391e-a351-4a41-9c30-84695e46c948" xlink:href="agnc-20220331.xsd#agnc_CreditRiskTransferSecuritiesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_InvestmentTypeCategorizationMember_25f43f1c-f731-4573-b22f-e4fd99beacfd" xlink:to="loc_agnc_CreditRiskTransferSecuritiesMember_4255391e-a351-4a41-9c30-84695e46c948" xlink:type="arc" order="3"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.agnc.com/role/InvestmentSecuritiesComponentsOfInvestmentSecuritiesDetails" xlink:type="simple" xlink:href="agnc-20220331.xsd#InvestmentSecuritiesComponentsOfInvestmentSecuritiesDetails"/>
  <link:definitionLink xlink:role="http://www.agnc.com/role/InvestmentSecuritiesComponentsOfInvestmentSecuritiesDetails" xlink:type="extended" id="i5a6fa23d9a514269af19a77779fdfad6_InvestmentSecuritiesComponentsOfInvestmentSecuritiesDetails">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfInvestmentsLineItems_a1118d81-949a-47e8-927b-d4631d8e5b72" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ScheduleOfInvestmentsLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_AvailableForSaleSecuritiesPar_79b95b6f-a796-4454-8375-20c048ec5444" xlink:href="agnc-20220331.xsd#agnc_AvailableForSaleSecuritiesPar"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ScheduleOfInvestmentsLineItems_a1118d81-949a-47e8-927b-d4631d8e5b72" xlink:to="loc_agnc_AvailableForSaleSecuritiesPar_79b95b6f-a796-4454-8375-20c048ec5444" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_DebtSecuritiesAvailableForSaleUnamortizedDiscount_eb31a1c9-36aa-45ed-8654-2e6ec01a17dc" xlink:href="agnc-20220331.xsd#agnc_DebtSecuritiesAvailableForSaleUnamortizedDiscount"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ScheduleOfInvestmentsLineItems_a1118d81-949a-47e8-927b-d4631d8e5b72" xlink:to="loc_agnc_DebtSecuritiesAvailableForSaleUnamortizedDiscount_eb31a1c9-36aa-45ed-8654-2e6ec01a17dc" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_DebtSecuritiesAvailableForSaleUnamortizedPremium_4a6a29cc-caa2-4d35-a997-4a95b13d8905" xlink:href="agnc-20220331.xsd#agnc_DebtSecuritiesAvailableForSaleUnamortizedPremium"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ScheduleOfInvestmentsLineItems_a1118d81-949a-47e8-927b-d4631d8e5b72" xlink:to="loc_agnc_DebtSecuritiesAvailableForSaleUnamortizedPremium_4a6a29cc-caa2-4d35-a997-4a95b13d8905" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis_b07c7f17-51ab-4be7-a4d9-8d9eebccf91a" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ScheduleOfInvestmentsLineItems_a1118d81-949a-47e8-927b-d4631d8e5b72" xlink:to="loc_us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis_b07c7f17-51ab-4be7-a4d9-8d9eebccf91a" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentUnamortizedDiscount_c3ece8ef-ac5f-4ed7-95b9-a5add717bd2a" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DebtInstrumentUnamortizedDiscount"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ScheduleOfInvestmentsLineItems_a1118d81-949a-47e8-927b-d4631d8e5b72" xlink:to="loc_us-gaap_DebtInstrumentUnamortizedDiscount_c3ece8ef-ac5f-4ed7-95b9-a5add717bd2a" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentUnamortizedPremium_8df2b438-48e1-42b4-bed7-c81c99465967" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DebtInstrumentUnamortizedPremium"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ScheduleOfInvestmentsLineItems_a1118d81-949a-47e8-927b-d4631d8e5b72" xlink:to="loc_us-gaap_DebtInstrumentUnamortizedPremium_8df2b438-48e1-42b4-bed7-c81c99465967" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtSecuritiesTradingUnrealizedGain_7ee0c36c-35b6-4f84-b18b-52d72015f6c6" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DebtSecuritiesTradingUnrealizedGain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ScheduleOfInvestmentsLineItems_a1118d81-949a-47e8-927b-d4631d8e5b72" xlink:to="loc_us-gaap_DebtSecuritiesTradingUnrealizedGain_7ee0c36c-35b6-4f84-b18b-52d72015f6c6" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtSecuritiesTradingUnrealizedLoss_64682b7c-aef6-4bc4-a024-13c4ee8e5f64" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DebtSecuritiesTradingUnrealizedLoss"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ScheduleOfInvestmentsLineItems_a1118d81-949a-47e8-927b-d4631d8e5b72" xlink:to="loc_us-gaap_DebtSecuritiesTradingUnrealizedLoss_64682b7c-aef6-4bc4-a024-13c4ee8e5f64" xlink:type="arc" order="7"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_TradingSecuritiesDebt_f6577d2f-eb5a-4ee7-b920-d9df1a111486" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_TradingSecuritiesDebt"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ScheduleOfInvestmentsLineItems_a1118d81-949a-47e8-927b-d4631d8e5b72" xlink:to="loc_us-gaap_TradingSecuritiesDebt_f6577d2f-eb5a-4ee7-b920-d9df1a111486" xlink:type="arc" order="8"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtSecuritiesTradingAndAvailableForSale_dfb1753c-ad9a-4828-80af-ea52f6e69178" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DebtSecuritiesTradingAndAvailableForSale"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ScheduleOfInvestmentsLineItems_a1118d81-949a-47e8-927b-d4631d8e5b72" xlink:to="loc_us-gaap_DebtSecuritiesTradingAndAvailableForSale_dfb1753c-ad9a-4828-80af-ea52f6e69178" xlink:type="arc" order="9"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AvailableForSaleSecuritiesAmortizedCost_4117f6c6-658c-414c-b524-7c8ab0b4e498" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AvailableForSaleSecuritiesAmortizedCost"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ScheduleOfInvestmentsLineItems_a1118d81-949a-47e8-927b-d4631d8e5b72" xlink:to="loc_us-gaap_AvailableForSaleSecuritiesAmortizedCost_4117f6c6-658c-414c-b524-7c8ab0b4e498" xlink:type="arc" order="10"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_DebtSecuritiesAvailableForSaleGrossUnrealizedLosses_fefbb7e9-8d05-4514-a00a-4fb1b357d1ab" xlink:href="agnc-20220331.xsd#agnc_DebtSecuritiesAvailableForSaleGrossUnrealizedLosses"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ScheduleOfInvestmentsLineItems_a1118d81-949a-47e8-927b-d4631d8e5b72" xlink:to="loc_agnc_DebtSecuritiesAvailableForSaleGrossUnrealizedLosses_fefbb7e9-8d05-4514-a00a-4fb1b357d1ab" xlink:type="arc" order="11"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_TradingSecuritiesCost_14b57092-1b89-4dcc-9268-51f326e46c73" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_TradingSecuritiesCost"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ScheduleOfInvestmentsLineItems_a1118d81-949a-47e8-927b-d4631d8e5b72" xlink:to="loc_us-gaap_TradingSecuritiesCost_14b57092-1b89-4dcc-9268-51f326e46c73" xlink:type="arc" order="12"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_DebtSecuritiesTradingSecuritiesGrossUnrealizedGains_c35bb23a-b6a9-4512-a70f-891bb4902cd8" xlink:href="agnc-20220331.xsd#agnc_DebtSecuritiesTradingSecuritiesGrossUnrealizedGains"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ScheduleOfInvestmentsLineItems_a1118d81-949a-47e8-927b-d4631d8e5b72" xlink:to="loc_agnc_DebtSecuritiesTradingSecuritiesGrossUnrealizedGains_c35bb23a-b6a9-4512-a70f-891bb4902cd8" xlink:type="arc" order="13"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_DebtSecuritiesTradingSecuritiesGrossUnrealizedLosses_38eee682-1705-47be-b8a8-2aafb8e8303b" xlink:href="agnc-20220331.xsd#agnc_DebtSecuritiesTradingSecuritiesGrossUnrealizedLosses"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ScheduleOfInvestmentsLineItems_a1118d81-949a-47e8-927b-d4631d8e5b72" xlink:to="loc_agnc_DebtSecuritiesTradingSecuritiesGrossUnrealizedLosses_38eee682-1705-47be-b8a8-2aafb8e8303b" xlink:type="arc" order="14"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AvailableForSaleSecuritiesGrossUnrealizedGains_195ab5ff-1c27-4991-a60f-6054e64a324e" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AvailableForSaleSecuritiesGrossUnrealizedGains"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ScheduleOfInvestmentsLineItems_a1118d81-949a-47e8-927b-d4631d8e5b72" xlink:to="loc_us-gaap_AvailableForSaleSecuritiesGrossUnrealizedGains_195ab5ff-1c27-4991-a60f-6054e64a324e" xlink:type="arc" order="15"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AvailableForSaleSecuritiesGrossUnrealizedLoss_989abcd4-0dca-47e0-b43e-fd84fec8e607" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AvailableForSaleSecuritiesGrossUnrealizedLoss"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ScheduleOfInvestmentsLineItems_a1118d81-949a-47e8-927b-d4631d8e5b72" xlink:to="loc_us-gaap_AvailableForSaleSecuritiesGrossUnrealizedLoss_989abcd4-0dca-47e0-b43e-fd84fec8e607" xlink:type="arc" order="16"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AvailableForSaleSecuritiesDebtSecurities_9f3002f1-a8c1-4b32-9e76-6182d2e46e40" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AvailableForSaleSecuritiesDebtSecurities"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ScheduleOfInvestmentsLineItems_a1118d81-949a-47e8-927b-d4631d8e5b72" xlink:to="loc_us-gaap_AvailableForSaleSecuritiesDebtSecurities_9f3002f1-a8c1-4b32-9e76-6182d2e46e40" xlink:type="arc" order="17"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_TradingSecuritiesPar_95978089-f3fa-41e9-a9cb-917b48dae79b" xlink:href="agnc-20220331.xsd#agnc_TradingSecuritiesPar"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ScheduleOfInvestmentsLineItems_a1118d81-949a-47e8-927b-d4631d8e5b72" xlink:to="loc_agnc_TradingSecuritiesPar_95978089-f3fa-41e9-a9cb-917b48dae79b" xlink:type="arc" order="18"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_DebtSecuritiesTradingSecuritiesUnamortizedDiscount_1ca9c649-00b1-42e0-8961-b0ffc8bc8708" xlink:href="agnc-20220331.xsd#agnc_DebtSecuritiesTradingSecuritiesUnamortizedDiscount"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ScheduleOfInvestmentsLineItems_a1118d81-949a-47e8-927b-d4631d8e5b72" xlink:to="loc_agnc_DebtSecuritiesTradingSecuritiesUnamortizedDiscount_1ca9c649-00b1-42e0-8961-b0ffc8bc8708" xlink:type="arc" order="19"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_DebtSecuritiesTradingSecuritiesUnamortizedPremium_622bde33-a603-4f50-ae6c-225251a8ba03" xlink:href="agnc-20220331.xsd#agnc_DebtSecuritiesTradingSecuritiesUnamortizedPremium"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ScheduleOfInvestmentsLineItems_a1118d81-949a-47e8-927b-d4631d8e5b72" xlink:to="loc_agnc_DebtSecuritiesTradingSecuritiesUnamortizedPremium_622bde33-a603-4f50-ae6c-225251a8ba03" xlink:type="arc" order="20"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_TradingSecuritiesDebtAmortizedCost_abf31975-1aa1-4fc2-b95e-0b0b2d11d0e2" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_TradingSecuritiesDebtAmortizedCost"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ScheduleOfInvestmentsLineItems_a1118d81-949a-47e8-927b-d4631d8e5b72" xlink:to="loc_us-gaap_TradingSecuritiesDebtAmortizedCost_abf31975-1aa1-4fc2-b95e-0b0b2d11d0e2" xlink:type="arc" order="21"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtWeightedAverageInterestRate_2f51c352-7d56-41d7-a86f-1aaf8eb6cb38" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DebtWeightedAverageInterestRate"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ScheduleOfInvestmentsLineItems_a1118d81-949a-47e8-927b-d4631d8e5b72" xlink:to="loc_us-gaap_DebtWeightedAverageInterestRate_2f51c352-7d56-41d7-a86f-1aaf8eb6cb38" xlink:type="arc" order="22"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_WeightedAverageYieldPercentage_c80fc3e3-0df2-4513-b0ae-f06cc157eaa4" xlink:href="agnc-20220331.xsd#agnc_WeightedAverageYieldPercentage"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ScheduleOfInvestmentsLineItems_a1118d81-949a-47e8-927b-d4631d8e5b72" xlink:to="loc_agnc_WeightedAverageYieldPercentage_c80fc3e3-0df2-4513-b0ae-f06cc157eaa4" xlink:type="arc" order="23"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_FuturePrepaymentRateAssumptionOfInvestmentPortfolio_8e6c691b-4730-40d7-a0c2-033e6763d4e9" xlink:href="agnc-20220331.xsd#agnc_FuturePrepaymentRateAssumptionOfInvestmentPortfolio"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ScheduleOfInvestmentsLineItems_a1118d81-949a-47e8-927b-d4631d8e5b72" xlink:to="loc_agnc_FuturePrepaymentRateAssumptionOfInvestmentPortfolio_8e6c691b-4730-40d7-a0c2-033e6763d4e9" xlink:type="arc" order="24"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_MortgageBackedSecuritiesAmortizedCost_9cea4ae4-2ed3-4968-8320-5443b935ef4c" xlink:href="agnc-20220331.xsd#agnc_MortgageBackedSecuritiesAmortizedCost"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ScheduleOfInvestmentsLineItems_a1118d81-949a-47e8-927b-d4631d8e5b72" xlink:to="loc_agnc_MortgageBackedSecuritiesAmortizedCost_9cea4ae4-2ed3-4968-8320-5443b935ef4c" xlink:type="arc" order="25"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_DebtSecuritiesAvailableForSaleGrossUnrealizedGains_362b6508-2c71-4ac1-b82f-9068515dc195" xlink:href="agnc-20220331.xsd#agnc_DebtSecuritiesAvailableForSaleGrossUnrealizedGains"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ScheduleOfInvestmentsLineItems_a1118d81-949a-47e8-927b-d4631d8e5b72" xlink:to="loc_agnc_DebtSecuritiesAvailableForSaleGrossUnrealizedGains_362b6508-2c71-4ac1-b82f-9068515dc195" xlink:type="arc" order="26"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfInvestmentsTable_f81d37a8-3403-479b-85c2-00321185428c" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ScheduleOfInvestmentsTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_ScheduleOfInvestmentsLineItems_a1118d81-949a-47e8-927b-d4631d8e5b72" xlink:to="loc_us-gaap_ScheduleOfInvestmentsTable_f81d37a8-3403-479b-85c2-00321185428c" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncomeStatementLocationAxis_13a27018-c67e-4535-9a8e-7a56f20e5714" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_IncomeStatementLocationAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfInvestmentsTable_f81d37a8-3403-479b-85c2-00321185428c" xlink:to="loc_us-gaap_IncomeStatementLocationAxis_13a27018-c67e-4535-9a8e-7a56f20e5714" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncomeStatementLocationDomain_13a27018-c67e-4535-9a8e-7a56f20e5714_default" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_IncomeStatementLocationDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_IncomeStatementLocationAxis_13a27018-c67e-4535-9a8e-7a56f20e5714" xlink:to="loc_us-gaap_IncomeStatementLocationDomain_13a27018-c67e-4535-9a8e-7a56f20e5714_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncomeStatementLocationDomain_1912b0a2-5cd5-4503-bc0d-253adbf26f1e" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_IncomeStatementLocationDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_IncomeStatementLocationAxis_13a27018-c67e-4535-9a8e-7a56f20e5714" xlink:to="loc_us-gaap_IncomeStatementLocationDomain_1912b0a2-5cd5-4503-bc0d-253adbf26f1e" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_InterestOnlyAndPrincipalOnlyStripMember_5bb3dd41-6709-4178-bc86-c6e1abfa25a8" xlink:href="agnc-20220331.xsd#agnc_InterestOnlyAndPrincipalOnlyStripMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncomeStatementLocationDomain_1912b0a2-5cd5-4503-bc0d-253adbf26f1e" xlink:to="loc_agnc_InterestOnlyAndPrincipalOnlyStripMember_5bb3dd41-6709-4178-bc86-c6e1abfa25a8" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_InvestmentTypeAxis_4afc70db-7a46-4b08-92ed-d9c4400ec457" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_InvestmentTypeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfInvestmentsTable_f81d37a8-3403-479b-85c2-00321185428c" xlink:to="loc_us-gaap_InvestmentTypeAxis_4afc70db-7a46-4b08-92ed-d9c4400ec457" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_InvestmentTypeCategorizationMember_4afc70db-7a46-4b08-92ed-d9c4400ec457_default" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_InvestmentTypeCategorizationMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_InvestmentTypeAxis_4afc70db-7a46-4b08-92ed-d9c4400ec457" xlink:to="loc_us-gaap_InvestmentTypeCategorizationMember_4afc70db-7a46-4b08-92ed-d9c4400ec457_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_InvestmentTypeCategorizationMember_6594abf6-b364-4b4d-adcc-b344df1ca87e" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_InvestmentTypeCategorizationMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_InvestmentTypeAxis_4afc70db-7a46-4b08-92ed-d9c4400ec457" xlink:to="loc_us-gaap_InvestmentTypeCategorizationMember_6594abf6-b364-4b4d-adcc-b344df1ca87e" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FederalNationalMortgageAssociationCertificatesAndObligationsFNMAMember_c582ffe5-ab58-4dd6-b35c-ed88ab8e149c" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FederalNationalMortgageAssociationCertificatesAndObligationsFNMAMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_InvestmentTypeCategorizationMember_6594abf6-b364-4b4d-adcc-b344df1ca87e" xlink:to="loc_us-gaap_FederalNationalMortgageAssociationCertificatesAndObligationsFNMAMember_c582ffe5-ab58-4dd6-b35c-ed88ab8e149c" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FederalHomeLoanMortgageCorporationCertificatesAndObligationsFHLMCMember_a1dfdfdd-a8ca-4e82-b536-66704880472f" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FederalHomeLoanMortgageCorporationCertificatesAndObligationsFHLMCMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_InvestmentTypeCategorizationMember_6594abf6-b364-4b4d-adcc-b344df1ca87e" xlink:to="loc_us-gaap_FederalHomeLoanMortgageCorporationCertificatesAndObligationsFHLMCMember_a1dfdfdd-a8ca-4e82-b536-66704880472f" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_GovernmentNationalMortgageAssociationCertificatesAndObligationsGNMAMember_2ced1904-2a01-4a35-9789-62e83e43c9af" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_GovernmentNationalMortgageAssociationCertificatesAndObligationsGNMAMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_InvestmentTypeCategorizationMember_6594abf6-b364-4b4d-adcc-b344df1ca87e" xlink:to="loc_us-gaap_GovernmentNationalMortgageAssociationCertificatesAndObligationsGNMAMember_2ced1904-2a01-4a35-9789-62e83e43c9af" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_MortgageBackedSecuritiesIssuedByPrivateEnterprisesMember_ba652c77-85ca-4fc0-adce-b66010989285" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_MortgageBackedSecuritiesIssuedByPrivateEnterprisesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_InvestmentTypeCategorizationMember_6594abf6-b364-4b4d-adcc-b344df1ca87e" xlink:to="loc_us-gaap_MortgageBackedSecuritiesIssuedByPrivateEnterprisesMember_ba652c77-85ca-4fc0-adce-b66010989285" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CommercialMortgageBackedSecuritiesMember_31046d59-46d1-4435-9966-3d2ddf8b2c4e" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_CommercialMortgageBackedSecuritiesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_InvestmentTypeCategorizationMember_6594abf6-b364-4b4d-adcc-b344df1ca87e" xlink:to="loc_us-gaap_CommercialMortgageBackedSecuritiesMember_31046d59-46d1-4435-9966-3d2ddf8b2c4e" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_CreditRiskTransferSecuritiesMember_9b86d6ae-c38a-4587-8207-a2fb9f5f262c" xlink:href="agnc-20220331.xsd#agnc_CreditRiskTransferSecuritiesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_InvestmentTypeCategorizationMember_6594abf6-b364-4b4d-adcc-b344df1ca87e" xlink:to="loc_agnc_CreditRiskTransferSecuritiesMember_9b86d6ae-c38a-4587-8207-a2fb9f5f262c" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FinancialInstrumentAxis_e8f075f0-84ac-4d29-a964-6c94cc4b2430" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FinancialInstrumentAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfInvestmentsTable_f81d37a8-3403-479b-85c2-00321185428c" xlink:to="loc_us-gaap_FinancialInstrumentAxis_e8f075f0-84ac-4d29-a964-6c94cc4b2430" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_e8f075f0-84ac-4d29-a964-6c94cc4b2430_default" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_FinancialInstrumentAxis_e8f075f0-84ac-4d29-a964-6c94cc4b2430" xlink:to="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_e8f075f0-84ac-4d29-a964-6c94cc4b2430_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_5fe8462a-b3df-4a7c-8c50-73b28151904d" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_FinancialInstrumentAxis_e8f075f0-84ac-4d29-a964-6c94cc4b2430" xlink:to="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_5fe8462a-b3df-4a7c-8c50-73b28151904d" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AvailableforsaleSecuritiesMember_9fd95de6-173f-4cec-b5b8-79ea5a436d59" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AvailableforsaleSecuritiesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_5fe8462a-b3df-4a7c-8c50-73b28151904d" xlink:to="loc_us-gaap_AvailableforsaleSecuritiesMember_9fd95de6-173f-4cec-b5b8-79ea5a436d59" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_TradingSecuritiesMember_f7004759-9170-41fa-9065-f8911b542445" xlink:href="agnc-20220331.xsd#agnc_TradingSecuritiesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_5fe8462a-b3df-4a7c-8c50-73b28151904d" xlink:to="loc_agnc_TradingSecuritiesMember_f7004759-9170-41fa-9065-f8911b542445" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_SecuritiesRemeasuredatFairValueMember_c1c53e5d-264b-4113-a8fc-b4a90afa35c3" xlink:href="agnc-20220331.xsd#agnc_SecuritiesRemeasuredatFairValueMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_5fe8462a-b3df-4a7c-8c50-73b28151904d" xlink:to="loc_agnc_SecuritiesRemeasuredatFairValueMember_c1c53e5d-264b-4113-a8fc-b4a90afa35c3" xlink:type="arc" order="2"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.agnc.com/role/InvestmentSecuritiesSummaryOfAgencySecuritiesEstimatedWeightedAverageLifeClassificationsDetails" xlink:type="simple" xlink:href="agnc-20220331.xsd#InvestmentSecuritiesSummaryOfAgencySecuritiesEstimatedWeightedAverageLifeClassificationsDetails"/>
  <link:definitionLink xlink:role="http://www.agnc.com/role/InvestmentSecuritiesSummaryOfAgencySecuritiesEstimatedWeightedAverageLifeClassificationsDetails" xlink:type="extended" id="iec0957eb605f4c348d4fa72098414f3f_InvestmentSecuritiesSummaryOfAgencySecuritiesEstimatedWeightedAverageLifeClassificationsDetails">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StatementLineItems_7e6e816b-bf7d-4739-9bf1-05a7d2a17088" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_StatementLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_AvailableForSaleSecuritiesWeightedAverageLifeFairValue_001187dc-7bba-4ab1-926b-23f911e2f8aa" xlink:href="agnc-20220331.xsd#agnc_AvailableForSaleSecuritiesWeightedAverageLifeFairValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_7e6e816b-bf7d-4739-9bf1-05a7d2a17088" xlink:to="loc_agnc_AvailableForSaleSecuritiesWeightedAverageLifeFairValue_001187dc-7bba-4ab1-926b-23f911e2f8aa" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_AvailableForSaleSecuritiesWeightedAverageLifeAmortizedCost_da6c2225-059e-4464-a5b7-2d2922b0a384" xlink:href="agnc-20220331.xsd#agnc_AvailableForSaleSecuritiesWeightedAverageLifeAmortizedCost"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_7e6e816b-bf7d-4739-9bf1-05a7d2a17088" xlink:to="loc_agnc_AvailableForSaleSecuritiesWeightedAverageLifeAmortizedCost_da6c2225-059e-4464-a5b7-2d2922b0a384" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_AvailableForSaleSecuritiesWeightedAverageLifeCouponRate_b6aa6bc8-8cd3-42a4-a266-9f89b8d4ddb5" xlink:href="agnc-20220331.xsd#agnc_AvailableForSaleSecuritiesWeightedAverageLifeCouponRate"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_7e6e816b-bf7d-4739-9bf1-05a7d2a17088" xlink:to="loc_agnc_AvailableForSaleSecuritiesWeightedAverageLifeCouponRate_b6aa6bc8-8cd3-42a4-a266-9f89b8d4ddb5" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_AvailableForSaleSecuritiesWeightedAverageLifeYield_27a6867b-7c80-44c4-ade8-c898014f41aa" xlink:href="agnc-20220331.xsd#agnc_AvailableForSaleSecuritiesWeightedAverageLifeYield"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_7e6e816b-bf7d-4739-9bf1-05a7d2a17088" xlink:to="loc_agnc_AvailableForSaleSecuritiesWeightedAverageLifeYield_27a6867b-7c80-44c4-ade8-c898014f41aa" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfTradingSecuritiesAndOtherTradingAssetsTable_c1190a4f-6bad-492e-b092-0496a6955c65" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ScheduleOfTradingSecuritiesAndOtherTradingAssetsTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_StatementLineItems_7e6e816b-bf7d-4739-9bf1-05a7d2a17088" xlink:to="loc_us-gaap_ScheduleOfTradingSecuritiesAndOtherTradingAssetsTable_c1190a4f-6bad-492e-b092-0496a6955c65" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FinancialInstrumentAxis_a08db66e-d213-40d2-a5e0-49284e638a34" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FinancialInstrumentAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfTradingSecuritiesAndOtherTradingAssetsTable_c1190a4f-6bad-492e-b092-0496a6955c65" xlink:to="loc_us-gaap_FinancialInstrumentAxis_a08db66e-d213-40d2-a5e0-49284e638a34" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_a08db66e-d213-40d2-a5e0-49284e638a34_default" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_FinancialInstrumentAxis_a08db66e-d213-40d2-a5e0-49284e638a34" xlink:to="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_a08db66e-d213-40d2-a5e0-49284e638a34_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_741557ef-8031-423b-ab15-da7f3d86e385" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_FinancialInstrumentAxis_a08db66e-d213-40d2-a5e0-49284e638a34" xlink:to="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_741557ef-8031-423b-ab15-da7f3d86e385" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_LessThanorEqualtoThreeYearsMember_22433106-32cf-452e-b1c7-b897a688201e" xlink:href="agnc-20220331.xsd#agnc_LessThanorEqualtoThreeYearsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_741557ef-8031-423b-ab15-da7f3d86e385" xlink:to="loc_agnc_LessThanorEqualtoThreeYearsMember_22433106-32cf-452e-b1c7-b897a688201e" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_GreaterThanThreeYearsAndLessThanOrEqualToFiveYearsMember_cdbe9a7a-66a9-48bc-8c3c-54519e553733" xlink:href="agnc-20220331.xsd#agnc_GreaterThanThreeYearsAndLessThanOrEqualToFiveYearsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_741557ef-8031-423b-ab15-da7f3d86e385" xlink:to="loc_agnc_GreaterThanThreeYearsAndLessThanOrEqualToFiveYearsMember_cdbe9a7a-66a9-48bc-8c3c-54519e553733" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_GreaterThanFiveYearsMember_9dd52a0e-5f3d-4444-abdb-37fa843ef8a8" xlink:href="agnc-20220331.xsd#agnc_GreaterThanFiveYearsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_741557ef-8031-423b-ab15-da7f3d86e385" xlink:to="loc_agnc_GreaterThanFiveYearsMember_9dd52a0e-5f3d-4444-abdb-37fa843ef8a8" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_GreaterThanTenYearsMember_13663d6d-c5c3-4fc1-a707-70c3eec51e80" xlink:href="agnc-20220331.xsd#agnc_GreaterThanTenYearsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_741557ef-8031-423b-ab15-da7f3d86e385" xlink:to="loc_agnc_GreaterThanTenYearsMember_13663d6d-c5c3-4fc1-a707-70c3eec51e80" xlink:type="arc" order="3"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.agnc.com/role/InvestmentSecuritiesSummaryOfChangesInAccumulatedOCIForAvailableForSaleSecurityDetails" xlink:type="simple" xlink:href="agnc-20220331.xsd#InvestmentSecuritiesSummaryOfChangesInAccumulatedOCIForAvailableForSaleSecurityDetails"/>
  <link:definitionLink xlink:role="http://www.agnc.com/role/InvestmentSecuritiesSummaryOfChangesInAccumulatedOCIForAvailableForSaleSecurityDetails" xlink:type="extended" id="idae64b2185834552a896bd898079f7f7_InvestmentSecuritiesSummaryOfChangesInAccumulatedOCIForAvailableForSaleSecurityDetails">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StatementLineItems_4cf02f63-45fb-4cca-a1a6-0e2b9adc6aa2" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_StatementLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_AccumulatedOtherComprehensiveIncomeLossRollForward_d9d9a183-bd11-497c-9c43-207d6e43d539" xlink:href="agnc-20220331.xsd#agnc_AccumulatedOtherComprehensiveIncomeLossRollForward"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_4cf02f63-45fb-4cca-a1a6-0e2b9adc6aa2" xlink:to="loc_agnc_AccumulatedOtherComprehensiveIncomeLossRollForward_d9d9a183-bd11-497c-9c43-207d6e43d539" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AccumulatedOtherComprehensiveIncomeLossAvailableForSaleSecuritiesAdjustmentNetOfTax_4551bf97-5307-4aee-8516-4e588e7d625e" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AccumulatedOtherComprehensiveIncomeLossAvailableForSaleSecuritiesAdjustmentNetOfTax"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_agnc_AccumulatedOtherComprehensiveIncomeLossRollForward_d9d9a183-bd11-497c-9c43-207d6e43d539" xlink:to="loc_us-gaap_AccumulatedOtherComprehensiveIncomeLossAvailableForSaleSecuritiesAdjustmentNetOfTax_4551bf97-5307-4aee-8516-4e588e7d625e" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherComprehensiveIncomeUnrealizedHoldingGainLossOnSecuritiesArisingDuringPeriodNetOfTax_fbf528b1-2140-4fa8-8bc5-c91114d1cf4f" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_OtherComprehensiveIncomeUnrealizedHoldingGainLossOnSecuritiesArisingDuringPeriodNetOfTax"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_agnc_AccumulatedOtherComprehensiveIncomeLossRollForward_d9d9a183-bd11-497c-9c43-207d6e43d539" xlink:to="loc_us-gaap_OtherComprehensiveIncomeUnrealizedHoldingGainLossOnSecuritiesArisingDuringPeriodNetOfTax_fbf528b1-2140-4fa8-8bc5-c91114d1cf4f" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_OtherComprehensiveIncomeReclassificationAdjustmentForSaleOfSecurityReversalOfPriorPeriodUnrealizedGainAndLossesOnRealization_63183ded-9418-450e-bf4f-15421d452dc2" xlink:href="agnc-20220331.xsd#agnc_OtherComprehensiveIncomeReclassificationAdjustmentForSaleOfSecurityReversalOfPriorPeriodUnrealizedGainAndLossesOnRealization"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_agnc_AccumulatedOtherComprehensiveIncomeLossRollForward_d9d9a183-bd11-497c-9c43-207d6e43d539" xlink:to="loc_agnc_OtherComprehensiveIncomeReclassificationAdjustmentForSaleOfSecurityReversalOfPriorPeriodUnrealizedGainAndLossesOnRealization_63183ded-9418-450e-bf4f-15421d452dc2" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AccumulatedOtherComprehensiveIncomeLossAvailableForSaleSecuritiesAdjustmentNetOfTax_1f081d55-bfc0-4db6-8aa7-7691cc90f14d" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AccumulatedOtherComprehensiveIncomeLossAvailableForSaleSecuritiesAdjustmentNetOfTax"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfTradingSecuritiesAndOtherTradingAssetsTable_9053a3e0-f044-4ff0-94ef-3198fc93b83a" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ScheduleOfTradingSecuritiesAndOtherTradingAssetsTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_StatementLineItems_4cf02f63-45fb-4cca-a1a6-0e2b9adc6aa2" xlink:to="loc_us-gaap_ScheduleOfTradingSecuritiesAndOtherTradingAssetsTable_9053a3e0-f044-4ff0-94ef-3198fc93b83a" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FinancialInstrumentAxis_23aba68c-1a2f-496f-ac59-d3d77f19d524" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FinancialInstrumentAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfTradingSecuritiesAndOtherTradingAssetsTable_9053a3e0-f044-4ff0-94ef-3198fc93b83a" xlink:to="loc_us-gaap_FinancialInstrumentAxis_23aba68c-1a2f-496f-ac59-d3d77f19d524" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_23aba68c-1a2f-496f-ac59-d3d77f19d524_default" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_FinancialInstrumentAxis_23aba68c-1a2f-496f-ac59-d3d77f19d524" xlink:to="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_23aba68c-1a2f-496f-ac59-d3d77f19d524_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_b48c1c3b-33a7-421f-bc88-bec8dfb515d0" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_FinancialInstrumentAxis_23aba68c-1a2f-496f-ac59-d3d77f19d524" xlink:to="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_b48c1c3b-33a7-421f-bc88-bec8dfb515d0" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AgencySecuritiesMember_ef6a455e-5aa6-4f68-acc1-7e8ad910872d" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AgencySecuritiesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_b48c1c3b-33a7-421f-bc88-bec8dfb515d0" xlink:to="loc_us-gaap_AgencySecuritiesMember_ef6a455e-5aa6-4f68-acc1-7e8ad910872d" xlink:type="arc" order="0"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.agnc.com/role/InvestmentSecuritiesSummaryOfContinuousUnrealizedLossPositionsOfAvailableForSaleSecurityDetails" xlink:type="simple" xlink:href="agnc-20220331.xsd#InvestmentSecuritiesSummaryOfContinuousUnrealizedLossPositionsOfAvailableForSaleSecurityDetails"/>
  <link:definitionLink xlink:role="http://www.agnc.com/role/InvestmentSecuritiesSummaryOfContinuousUnrealizedLossPositionsOfAvailableForSaleSecurityDetails" xlink:type="extended" id="ie49d1b1513504d3dac5254c1dad5b423_InvestmentSecuritiesSummaryOfContinuousUnrealizedLossPositionsOfAvailableForSaleSecurityDetails">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StatementLineItems_3d81c001-b963-4ed2-8020-537ce9cf5c4d" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_StatementLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionLessThanTwelveMonthsFairValue_179ef0be-cf1c-43d2-8e46-877ebc0b486c" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionLessThanTwelveMonthsFairValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_3d81c001-b963-4ed2-8020-537ce9cf5c4d" xlink:to="loc_us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionLessThanTwelveMonthsFairValue_179ef0be-cf1c-43d2-8e46-877ebc0b486c" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsAccumulatedLoss_cb106630-09dc-489e-8dc4-a2380c50becd" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsAccumulatedLoss"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_3d81c001-b963-4ed2-8020-537ce9cf5c4d" xlink:to="loc_us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsAccumulatedLoss_cb106630-09dc-489e-8dc4-a2380c50becd" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionTwelveMonthsOrLongerFairValue_e3ec5939-51b4-48df-a648-70d5d144f468" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionTwelveMonthsOrLongerFairValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_3d81c001-b963-4ed2-8020-537ce9cf5c4d" xlink:to="loc_us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionTwelveMonthsOrLongerFairValue_e3ec5939-51b4-48df-a648-70d5d144f468" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLongerAccumulatedLoss_6557f61b-4ff7-4f93-a287-cf89b1438f56" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLongerAccumulatedLoss"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_3d81c001-b963-4ed2-8020-537ce9cf5c4d" xlink:to="loc_us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLongerAccumulatedLoss_6557f61b-4ff7-4f93-a287-cf89b1438f56" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionFairValue_6b093e32-928b-4109-93cc-f398345fad25" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionFairValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_3d81c001-b963-4ed2-8020-537ce9cf5c4d" xlink:to="loc_us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionFairValue_6b093e32-928b-4109-93cc-f398345fad25" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtSecuritiesAvailableForSaleUnrealizedLossPositionAccumulatedLoss_e61d0b1a-1e47-4a05-b5db-abc054bddf0c" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DebtSecuritiesAvailableForSaleUnrealizedLossPositionAccumulatedLoss"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_3d81c001-b963-4ed2-8020-537ce9cf5c4d" xlink:to="loc_us-gaap_DebtSecuritiesAvailableForSaleUnrealizedLossPositionAccumulatedLoss_e61d0b1a-1e47-4a05-b5db-abc054bddf0c" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12Months_51464aa4-81e1-4d0d-939e-f2a75c4e46a2" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12Months"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_3d81c001-b963-4ed2-8020-537ce9cf5c4d" xlink:to="loc_us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12Months_51464aa4-81e1-4d0d-939e-f2a75c4e46a2" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLonger_38f95b6a-d0a8-4ce9-a44c-19d225d82aaa" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLonger"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_3d81c001-b963-4ed2-8020-537ce9cf5c4d" xlink:to="loc_us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLonger_38f95b6a-d0a8-4ce9-a44c-19d225d82aaa" xlink:type="arc" order="7"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtSecuritiesAvailableForSaleUnrealizedLossPosition_4645d4e9-43c1-4a04-9f74-c1a56285cd15" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DebtSecuritiesAvailableForSaleUnrealizedLossPosition"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_3d81c001-b963-4ed2-8020-537ce9cf5c4d" xlink:to="loc_us-gaap_DebtSecuritiesAvailableForSaleUnrealizedLossPosition_4645d4e9-43c1-4a04-9f74-c1a56285cd15" xlink:type="arc" order="8"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StatementTable_64545e7f-286a-4411-9fb2-beb095bc6358" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_StatementTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_StatementLineItems_3d81c001-b963-4ed2-8020-537ce9cf5c4d" xlink:to="loc_us-gaap_StatementTable_64545e7f-286a-4411-9fb2-beb095bc6358" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StatementEquityComponentsAxis_6b315d0c-0287-4731-83a6-557c78186caf" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_StatementEquityComponentsAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_StatementTable_64545e7f-286a-4411-9fb2-beb095bc6358" xlink:to="loc_us-gaap_StatementEquityComponentsAxis_6b315d0c-0287-4731-83a6-557c78186caf" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EquityComponentDomain_6b315d0c-0287-4731-83a6-557c78186caf_default" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_EquityComponentDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_StatementEquityComponentsAxis_6b315d0c-0287-4731-83a6-557c78186caf" xlink:to="loc_us-gaap_EquityComponentDomain_6b315d0c-0287-4731-83a6-557c78186caf_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EquityComponentDomain_27e33523-40f7-4fa3-ab81-f1a6f291c3a5" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_EquityComponentDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_StatementEquityComponentsAxis_6b315d0c-0287-4731-83a6-557c78186caf" xlink:to="loc_us-gaap_EquityComponentDomain_27e33523-40f7-4fa3-ab81-f1a6f291c3a5" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AccumulatedOtherComprehensiveIncomeMember_6602bd1a-ae68-4bf3-a7ed-cee476249ad2" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AccumulatedOtherComprehensiveIncomeMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EquityComponentDomain_27e33523-40f7-4fa3-ab81-f1a6f291c3a5" xlink:to="loc_us-gaap_AccumulatedOtherComprehensiveIncomeMember_6602bd1a-ae68-4bf3-a7ed-cee476249ad2" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FinancialInstrumentAxis_1e7ef467-6009-44d1-9e43-640c756092a5" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FinancialInstrumentAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_StatementTable_64545e7f-286a-4411-9fb2-beb095bc6358" xlink:to="loc_us-gaap_FinancialInstrumentAxis_1e7ef467-6009-44d1-9e43-640c756092a5" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_1e7ef467-6009-44d1-9e43-640c756092a5_default" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_FinancialInstrumentAxis_1e7ef467-6009-44d1-9e43-640c756092a5" xlink:to="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_1e7ef467-6009-44d1-9e43-640c756092a5_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_c6a73e26-fbad-4121-8b6b-7fd3082cbaee" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_FinancialInstrumentAxis_1e7ef467-6009-44d1-9e43-640c756092a5" xlink:to="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_c6a73e26-fbad-4121-8b6b-7fd3082cbaee" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_MortgageBackedSecuritiesIssuedByUSGovernmentSponsoredEnterprisesMember_d59d37fc-3871-425d-aa14-d64753c18f29" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_MortgageBackedSecuritiesIssuedByUSGovernmentSponsoredEnterprisesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_c6a73e26-fbad-4121-8b6b-7fd3082cbaee" xlink:to="loc_us-gaap_MortgageBackedSecuritiesIssuedByUSGovernmentSponsoredEnterprisesMember_d59d37fc-3871-425d-aa14-d64753c18f29" xlink:type="arc" order="0"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.agnc.com/role/InvestmentSecuritiesSummaryOfNetGainFromSaleOfAgencySecuritiesDetails" xlink:type="simple" xlink:href="agnc-20220331.xsd#InvestmentSecuritiesSummaryOfNetGainFromSaleOfAgencySecuritiesDetails"/>
  <link:definitionLink xlink:role="http://www.agnc.com/role/InvestmentSecuritiesSummaryOfNetGainFromSaleOfAgencySecuritiesDetails" xlink:type="extended" id="ie5cd5f12d337424a8516bf4c8d121375_InvestmentSecuritiesSummaryOfNetGainFromSaleOfAgencySecuritiesDetails">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StatementLineItems_5dc5a1cd-a74d-4a57-b9cb-26d7da364b85" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_StatementLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_GainLossOnOtherDebt_ef1afe5e-68b9-451e-a18a-99aec40bfad6" xlink:href="agnc-20220331.xsd#agnc_GainLossOnOtherDebt"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_5dc5a1cd-a74d-4a57-b9cb-26d7da364b85" xlink:to="loc_agnc_GainLossOnOtherDebt_ef1afe5e-68b9-451e-a18a-99aec40bfad6" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_CostOfSaleOfAvailableForSaleSecuities_15c18618-0ac1-4373-9150-70d05134150b" xlink:href="agnc-20220331.xsd#agnc_CostOfSaleOfAvailableForSaleSecuities"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_5dc5a1cd-a74d-4a57-b9cb-26d7da364b85" xlink:to="loc_agnc_CostOfSaleOfAvailableForSaleSecuities_15c18618-0ac1-4373-9150-70d05134150b" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_CostofSaleofFairValueOptionSecurities_9fc546a9-77ee-4a12-add5-9707524a257d" xlink:href="agnc-20220331.xsd#agnc_CostofSaleofFairValueOptionSecurities"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_5dc5a1cd-a74d-4a57-b9cb-26d7da364b85" xlink:to="loc_agnc_CostofSaleofFairValueOptionSecurities_9fc546a9-77ee-4a12-add5-9707524a257d" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_CostofSaleofInvestmentSecurities_c3e88d72-f8e0-443b-aab0-6e24692c3640" xlink:href="agnc-20220331.xsd#agnc_CostofSaleofInvestmentSecurities"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_5dc5a1cd-a74d-4a57-b9cb-26d7da364b85" xlink:to="loc_agnc_CostofSaleofInvestmentSecurities_c3e88d72-f8e0-443b-aab0-6e24692c3640" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_ProceedsFromSaleOfDebtSecurities_1925bd5f-ff2e-4837-9818-ef77f424b732" xlink:href="agnc-20220331.xsd#agnc_ProceedsFromSaleOfDebtSecurities"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_5dc5a1cd-a74d-4a57-b9cb-26d7da364b85" xlink:to="loc_agnc_ProceedsFromSaleOfDebtSecurities_1925bd5f-ff2e-4837-9818-ef77f424b732" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_ProceedsFromSaleOfDebtSecuritiesTrading_e76a9745-e2f5-42d3-8984-75e28227bde9" xlink:href="agnc-20220331.xsd#agnc_ProceedsFromSaleOfDebtSecuritiesTrading"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_5dc5a1cd-a74d-4a57-b9cb-26d7da364b85" xlink:to="loc_agnc_ProceedsFromSaleOfDebtSecuritiesTrading_e76a9745-e2f5-42d3-8984-75e28227bde9" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ProceedsFromSaleOfAvailableForSaleSecuritiesDebt_0060ad3b-ff0f-4a10-b3af-2b116d28ffd5" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ProceedsFromSaleOfAvailableForSaleSecuritiesDebt"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_5dc5a1cd-a74d-4a57-b9cb-26d7da364b85" xlink:to="loc_us-gaap_ProceedsFromSaleOfAvailableForSaleSecuritiesDebt_0060ad3b-ff0f-4a10-b3af-2b116d28ffd5" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ProceedsFromSaleOfAvailableForSaleSecurities_b524209c-fe54-426e-ba60-f644fc054e3e" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ProceedsFromSaleOfAvailableForSaleSecurities"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_5dc5a1cd-a74d-4a57-b9cb-26d7da364b85" xlink:to="loc_us-gaap_ProceedsFromSaleOfAvailableForSaleSecurities_b524209c-fe54-426e-ba60-f644fc054e3e" xlink:type="arc" order="7"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_GainLossOnSalesOfMortgageBackedSecuritiesMBS_3ac5dcdd-865d-441e-8396-4209c9beb99f" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_GainLossOnSalesOfMortgageBackedSecuritiesMBS"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_5dc5a1cd-a74d-4a57-b9cb-26d7da364b85" xlink:to="loc_us-gaap_GainLossOnSalesOfMortgageBackedSecuritiesMBS_3ac5dcdd-865d-441e-8396-4209c9beb99f" xlink:type="arc" order="8"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtSecuritiesAvailableForSaleRealizedGain_c2c82fc3-3d0c-44e1-9529-bcf99ea06f84" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DebtSecuritiesAvailableForSaleRealizedGain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_5dc5a1cd-a74d-4a57-b9cb-26d7da364b85" xlink:to="loc_us-gaap_DebtSecuritiesAvailableForSaleRealizedGain_c2c82fc3-3d0c-44e1-9529-bcf99ea06f84" xlink:type="arc" order="9"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtSecuritiesAvailableForSaleRealizedLoss_d49bac67-65f2-4308-9640-ae2d582235b3" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DebtSecuritiesAvailableForSaleRealizedLoss"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_5dc5a1cd-a74d-4a57-b9cb-26d7da364b85" xlink:to="loc_us-gaap_DebtSecuritiesAvailableForSaleRealizedLoss_d49bac67-65f2-4308-9640-ae2d582235b3" xlink:type="arc" order="10"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AvailableForSaleSecuritiesGrossRealizedLosses_bde6847b-0558-4b8d-9905-374aa5550dbc" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AvailableForSaleSecuritiesGrossRealizedLosses"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_5dc5a1cd-a74d-4a57-b9cb-26d7da364b85" xlink:to="loc_us-gaap_AvailableForSaleSecuritiesGrossRealizedLosses_bde6847b-0558-4b8d-9905-374aa5550dbc" xlink:type="arc" order="11"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfTradingSecuritiesAndOtherTradingAssetsTable_beb9b9d3-9bed-422c-908d-3d3ed103146c" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ScheduleOfTradingSecuritiesAndOtherTradingAssetsTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_StatementLineItems_5dc5a1cd-a74d-4a57-b9cb-26d7da364b85" xlink:to="loc_us-gaap_ScheduleOfTradingSecuritiesAndOtherTradingAssetsTable_beb9b9d3-9bed-422c-908d-3d3ed103146c" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_InvestmentTypeAxis_7390995e-97b3-4c0c-aca9-323b93fe6e74" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_InvestmentTypeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfTradingSecuritiesAndOtherTradingAssetsTable_beb9b9d3-9bed-422c-908d-3d3ed103146c" xlink:to="loc_us-gaap_InvestmentTypeAxis_7390995e-97b3-4c0c-aca9-323b93fe6e74" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_InvestmentTypeCategorizationMember_7390995e-97b3-4c0c-aca9-323b93fe6e74_default" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_InvestmentTypeCategorizationMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_InvestmentTypeAxis_7390995e-97b3-4c0c-aca9-323b93fe6e74" xlink:to="loc_us-gaap_InvestmentTypeCategorizationMember_7390995e-97b3-4c0c-aca9-323b93fe6e74_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_InvestmentTypeCategorizationMember_e9e8fae3-f665-44f1-80b3-46daec89e725" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_InvestmentTypeCategorizationMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_InvestmentTypeAxis_7390995e-97b3-4c0c-aca9-323b93fe6e74" xlink:to="loc_us-gaap_InvestmentTypeCategorizationMember_e9e8fae3-f665-44f1-80b3-46daec89e725" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_CostandProceedsofInvestmentSecuritiesMember_5888d99f-affd-4475-bfd0-c6307acc9daa" xlink:href="agnc-20220331.xsd#agnc_CostandProceedsofInvestmentSecuritiesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_InvestmentTypeCategorizationMember_e9e8fae3-f665-44f1-80b3-46daec89e725" xlink:to="loc_agnc_CostandProceedsofInvestmentSecuritiesMember_5888d99f-affd-4475-bfd0-c6307acc9daa" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_GrossGainLossofInvestmentSecuritiesMember_bd509970-ef65-4bfe-93f1-ea320f79ac6e" xlink:href="agnc-20220331.xsd#agnc_GrossGainLossofInvestmentSecuritiesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_InvestmentTypeCategorizationMember_e9e8fae3-f665-44f1-80b3-46daec89e725" xlink:to="loc_agnc_GrossGainLossofInvestmentSecuritiesMember_bd509970-ef65-4bfe-93f1-ea320f79ac6e" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncomeStatementLocationAxis_919b99df-4129-4f96-9405-4a0160764045" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_IncomeStatementLocationAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfTradingSecuritiesAndOtherTradingAssetsTable_beb9b9d3-9bed-422c-908d-3d3ed103146c" xlink:to="loc_us-gaap_IncomeStatementLocationAxis_919b99df-4129-4f96-9405-4a0160764045" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncomeStatementLocationDomain_919b99df-4129-4f96-9405-4a0160764045_default" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_IncomeStatementLocationDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_IncomeStatementLocationAxis_919b99df-4129-4f96-9405-4a0160764045" xlink:to="loc_us-gaap_IncomeStatementLocationDomain_919b99df-4129-4f96-9405-4a0160764045_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncomeStatementLocationDomain_5159c404-b463-48e1-8c6e-c52215196dd0" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_IncomeStatementLocationDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_IncomeStatementLocationAxis_919b99df-4129-4f96-9405-4a0160764045" xlink:to="loc_us-gaap_IncomeStatementLocationDomain_5159c404-b463-48e1-8c6e-c52215196dd0" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_InterestOnlyAndPrincipalOnlyStripMember_87d6c36d-d739-4ee6-a218-552985aee61b" xlink:href="agnc-20220331.xsd#agnc_InterestOnlyAndPrincipalOnlyStripMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncomeStatementLocationDomain_5159c404-b463-48e1-8c6e-c52215196dd0" xlink:to="loc_agnc_InterestOnlyAndPrincipalOnlyStripMember_87d6c36d-d739-4ee6-a218-552985aee61b" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_UnderlyingAssetClassAxis_492fada4-8575-46d3-93e5-aaeb9c8add2d" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_UnderlyingAssetClassAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfTradingSecuritiesAndOtherTradingAssetsTable_beb9b9d3-9bed-422c-908d-3d3ed103146c" xlink:to="loc_us-gaap_UnderlyingAssetClassAxis_492fada4-8575-46d3-93e5-aaeb9c8add2d" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_UnderlyingAssetClassDomain_492fada4-8575-46d3-93e5-aaeb9c8add2d_default" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_UnderlyingAssetClassDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_UnderlyingAssetClassAxis_492fada4-8575-46d3-93e5-aaeb9c8add2d" xlink:to="loc_us-gaap_UnderlyingAssetClassDomain_492fada4-8575-46d3-93e5-aaeb9c8add2d_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_UnderlyingAssetClassDomain_4c9d0c2b-5ed4-4e62-b988-eae6bfbc41cf" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_UnderlyingAssetClassDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_UnderlyingAssetClassAxis_492fada4-8575-46d3-93e5-aaeb9c8add2d" xlink:to="loc_us-gaap_UnderlyingAssetClassDomain_4c9d0c2b-5ed4-4e62-b988-eae6bfbc41cf" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AvailableforsaleSecuritiesMember_e0c629e5-afcb-4f3f-b622-47099a868a3e" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AvailableforsaleSecuritiesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_UnderlyingAssetClassDomain_4c9d0c2b-5ed4-4e62-b988-eae6bfbc41cf" xlink:to="loc_us-gaap_AvailableforsaleSecuritiesMember_e0c629e5-afcb-4f3f-b622-47099a868a3e" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_SecuritiesRemeasuredatFairValueMember_67fdd37b-399d-4a24-bce0-d46275c76f49" xlink:href="agnc-20220331.xsd#agnc_SecuritiesRemeasuredatFairValueMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_UnderlyingAssetClassDomain_4c9d0c2b-5ed4-4e62-b988-eae6bfbc41cf" xlink:to="loc_agnc_SecuritiesRemeasuredatFairValueMember_67fdd37b-399d-4a24-bce0-d46275c76f49" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SecuritiesAssetsMember_5e8ebc91-4031-4038-9bee-2654ccb80ce6" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_SecuritiesAssetsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_UnderlyingAssetClassDomain_4c9d0c2b-5ed4-4e62-b988-eae6bfbc41cf" xlink:to="loc_us-gaap_SecuritiesAssetsMember_5e8ebc91-4031-4038-9bee-2654ccb80ce6" xlink:type="arc" order="2"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.agnc.com/role/InvestmentSecuritiesSecuritiesbyCreditRatingDetails" xlink:type="simple" xlink:href="agnc-20220331.xsd#InvestmentSecuritiesSecuritiesbyCreditRatingDetails"/>
  <link:definitionLink xlink:role="http://www.agnc.com/role/InvestmentSecuritiesSecuritiesbyCreditRatingDetails" xlink:type="extended" id="i4fec8027e96c4eba87ca479bd6026922_InvestmentSecuritiesSecuritiesbyCreditRatingDetails">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems_a03da38f-644a-42be-bb99-3321e3be8bae" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_TradingSecuritiesDebt_835053ff-afdc-499b-ab5f-34a0f6957b0a" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_TradingSecuritiesDebt"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems_a03da38f-644a-42be-bb99-3321e3be8bae" xlink:to="loc_us-gaap_TradingSecuritiesDebt_835053ff-afdc-499b-ab5f-34a0f6957b0a" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtSecuritiesTradingAndAvailableForSale_d5d82537-0580-4e0c-a011-0464c25c3605" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DebtSecuritiesTradingAndAvailableForSale"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems_a03da38f-644a-42be-bb99-3321e3be8bae" xlink:to="loc_us-gaap_DebtSecuritiesTradingAndAvailableForSale_d5d82537-0580-4e0c-a011-0464c25c3605" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfAvailableForSaleSecuritiesTable_5644e33b-e881-42f5-be23-03812111a1cf" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ScheduleOfAvailableForSaleSecuritiesTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems_a03da38f-644a-42be-bb99-3321e3be8bae" xlink:to="loc_us-gaap_ScheduleOfAvailableForSaleSecuritiesTable_5644e33b-e881-42f5-be23-03812111a1cf" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_CreditRatingAxis_d0823eb7-d87f-4f5a-a74e-be9e0886e8c5" xlink:href="agnc-20220331.xsd#agnc_CreditRatingAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfAvailableForSaleSecuritiesTable_5644e33b-e881-42f5-be23-03812111a1cf" xlink:to="loc_agnc_CreditRatingAxis_d0823eb7-d87f-4f5a-a74e-be9e0886e8c5" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_CreditRatingDomain_d0823eb7-d87f-4f5a-a74e-be9e0886e8c5_default" xlink:href="agnc-20220331.xsd#agnc_CreditRatingDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_agnc_CreditRatingAxis_d0823eb7-d87f-4f5a-a74e-be9e0886e8c5" xlink:to="loc_agnc_CreditRatingDomain_d0823eb7-d87f-4f5a-a74e-be9e0886e8c5_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_CreditRatingDomain_e2293293-356e-447c-9d67-9c09ab1f5876" xlink:href="agnc-20220331.xsd#agnc_CreditRatingDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_agnc_CreditRatingAxis_d0823eb7-d87f-4f5a-a74e-be9e0886e8c5" xlink:to="loc_agnc_CreditRatingDomain_e2293293-356e-447c-9d67-9c09ab1f5876" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_BBBRatingMember_d59d4f61-19a1-4543-94b6-88f0acc2f2d0" xlink:href="agnc-20220331.xsd#agnc_BBBRatingMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_agnc_CreditRatingDomain_e2293293-356e-447c-9d67-9c09ab1f5876" xlink:to="loc_agnc_BBBRatingMember_d59d4f61-19a1-4543-94b6-88f0acc2f2d0" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_BBRatingMember_b280ea95-3d0c-48f4-9eaa-333368a307aa" xlink:href="agnc-20220331.xsd#agnc_BBRatingMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_agnc_CreditRatingDomain_e2293293-356e-447c-9d67-9c09ab1f5876" xlink:to="loc_agnc_BBRatingMember_b280ea95-3d0c-48f4-9eaa-333368a307aa" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_AAARatingMember_534df20e-75c7-4d89-8a3f-a25020f79855" xlink:href="agnc-20220331.xsd#agnc_AAARatingMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_agnc_CreditRatingDomain_e2293293-356e-447c-9d67-9c09ab1f5876" xlink:to="loc_agnc_AAARatingMember_534df20e-75c7-4d89-8a3f-a25020f79855" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_AARatingMember_0407415b-d0a0-498e-8b10-3a301c1b9a38" xlink:href="agnc-20220331.xsd#agnc_AARatingMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_agnc_CreditRatingDomain_e2293293-356e-447c-9d67-9c09ab1f5876" xlink:to="loc_agnc_AARatingMember_0407415b-d0a0-498e-8b10-3a301c1b9a38" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_ARatingMember_e1328a7c-d627-4628-a9fc-9710bad94d8b" xlink:href="agnc-20220331.xsd#agnc_ARatingMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_agnc_CreditRatingDomain_e2293293-356e-447c-9d67-9c09ab1f5876" xlink:to="loc_agnc_ARatingMember_e1328a7c-d627-4628-a9fc-9710bad94d8b" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_BRatingMember_83d744a9-929b-4c03-9f3f-b2aa7adba92d" xlink:href="agnc-20220331.xsd#agnc_BRatingMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_agnc_CreditRatingDomain_e2293293-356e-447c-9d67-9c09ab1f5876" xlink:to="loc_agnc_BRatingMember_83d744a9-929b-4c03-9f3f-b2aa7adba92d" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_NotRatedMember_70c2a07e-4457-4cc4-8a80-f17fed889bd7" xlink:href="agnc-20220331.xsd#agnc_NotRatedMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_agnc_CreditRatingDomain_e2293293-356e-447c-9d67-9c09ab1f5876" xlink:to="loc_agnc_NotRatedMember_70c2a07e-4457-4cc4-8a80-f17fed889bd7" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FinancialInstrumentAxis_301881c0-2d58-42ef-88de-6faaa94a81fd" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FinancialInstrumentAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfAvailableForSaleSecuritiesTable_5644e33b-e881-42f5-be23-03812111a1cf" xlink:to="loc_us-gaap_FinancialInstrumentAxis_301881c0-2d58-42ef-88de-6faaa94a81fd" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_301881c0-2d58-42ef-88de-6faaa94a81fd_default" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_FinancialInstrumentAxis_301881c0-2d58-42ef-88de-6faaa94a81fd" xlink:to="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_301881c0-2d58-42ef-88de-6faaa94a81fd_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_e4a6d037-78c1-4785-97f2-1a4800b350e6" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_FinancialInstrumentAxis_301881c0-2d58-42ef-88de-6faaa94a81fd" xlink:to="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_e4a6d037-78c1-4785-97f2-1a4800b350e6" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_SecuritiesRemeasuredatFairValueMember_76703374-bb1b-4627-bd9d-3a5f738dc179" xlink:href="agnc-20220331.xsd#agnc_SecuritiesRemeasuredatFairValueMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_e4a6d037-78c1-4785-97f2-1a4800b350e6" xlink:to="loc_agnc_SecuritiesRemeasuredatFairValueMember_76703374-bb1b-4627-bd9d-3a5f738dc179" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AvailableforsaleSecuritiesMember_7df31901-239d-4326-a83d-64538ea0f2a6" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AvailableforsaleSecuritiesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_e4a6d037-78c1-4785-97f2-1a4800b350e6" xlink:to="loc_us-gaap_AvailableforsaleSecuritiesMember_7df31901-239d-4326-a83d-64538ea0f2a6" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_AgencySecuritiesRemeasuredAtFairValueThroughEarningsMember_5acde872-71d9-4d31-851c-b6779e863e44" xlink:href="agnc-20220331.xsd#agnc_AgencySecuritiesRemeasuredAtFairValueThroughEarningsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_e4a6d037-78c1-4785-97f2-1a4800b350e6" xlink:to="loc_agnc_AgencySecuritiesRemeasuredAtFairValueThroughEarningsMember_5acde872-71d9-4d31-851c-b6779e863e44" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_InvestmentTypeAxis_39d49578-fef8-44e4-bfa6-d224ea705052" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_InvestmentTypeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfAvailableForSaleSecuritiesTable_5644e33b-e881-42f5-be23-03812111a1cf" xlink:to="loc_us-gaap_InvestmentTypeAxis_39d49578-fef8-44e4-bfa6-d224ea705052" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_InvestmentTypeCategorizationMember_39d49578-fef8-44e4-bfa6-d224ea705052_default" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_InvestmentTypeCategorizationMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_InvestmentTypeAxis_39d49578-fef8-44e4-bfa6-d224ea705052" xlink:to="loc_us-gaap_InvestmentTypeCategorizationMember_39d49578-fef8-44e4-bfa6-d224ea705052_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_InvestmentTypeCategorizationMember_cd6d4f43-9d98-44c0-a71e-e11bd3849fbc" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_InvestmentTypeCategorizationMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_InvestmentTypeAxis_39d49578-fef8-44e4-bfa6-d224ea705052" xlink:to="loc_us-gaap_InvestmentTypeCategorizationMember_cd6d4f43-9d98-44c0-a71e-e11bd3849fbc" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_MortgageBackedSecuritiesIssuedByPrivateEnterprisesMember_54f9276d-5dd6-4129-baa9-69fdb493581a" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_MortgageBackedSecuritiesIssuedByPrivateEnterprisesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_InvestmentTypeCategorizationMember_cd6d4f43-9d98-44c0-a71e-e11bd3849fbc" xlink:to="loc_us-gaap_MortgageBackedSecuritiesIssuedByPrivateEnterprisesMember_54f9276d-5dd6-4129-baa9-69fdb493581a" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CommercialMortgageBackedSecuritiesMember_3feb6ad5-fb02-42bb-b0de-a3323b5355db" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_CommercialMortgageBackedSecuritiesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_InvestmentTypeCategorizationMember_cd6d4f43-9d98-44c0-a71e-e11bd3849fbc" xlink:to="loc_us-gaap_CommercialMortgageBackedSecuritiesMember_3feb6ad5-fb02-42bb-b0de-a3323b5355db" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_CreditRiskTransferSecuritiesMember_49f3c3c2-b572-4faf-83d7-239e38665f14" xlink:href="agnc-20220331.xsd#agnc_CreditRiskTransferSecuritiesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_InvestmentTypeCategorizationMember_cd6d4f43-9d98-44c0-a71e-e11bd3849fbc" xlink:to="loc_agnc_CreditRiskTransferSecuritiesMember_49f3c3c2-b572-4faf-83d7-239e38665f14" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeAxis_b86e3709-9a7c-4683-a9b2-bd21b5128de9" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_RangeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfAvailableForSaleSecuritiesTable_5644e33b-e881-42f5-be23-03812111a1cf" xlink:to="loc_srt_RangeAxis_b86e3709-9a7c-4683-a9b2-bd21b5128de9" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeMember_b86e3709-9a7c-4683-a9b2-bd21b5128de9_default" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_RangeMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_RangeAxis_b86e3709-9a7c-4683-a9b2-bd21b5128de9" xlink:to="loc_srt_RangeMember_b86e3709-9a7c-4683-a9b2-bd21b5128de9_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeMember_9e82e79d-8bf6-4e8b-9f48-9707e9709b20" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_RangeMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_RangeAxis_b86e3709-9a7c-4683-a9b2-bd21b5128de9" xlink:to="loc_srt_RangeMember_9e82e79d-8bf6-4e8b-9f48-9707e9709b20" xlink:type="arc" order="1"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.agnc.com/role/RepurchaseAgreementsAndReverseRepurchaseAgreementsNarrativeDetails" xlink:type="simple" xlink:href="agnc-20220331.xsd#RepurchaseAgreementsAndReverseRepurchaseAgreementsNarrativeDetails"/>
  <link:definitionLink xlink:role="http://www.agnc.com/role/RepurchaseAgreementsAndReverseRepurchaseAgreementsNarrativeDetails" xlink:type="extended" id="i866811134ee0416490d56874b7701126_RepurchaseAgreementsAndReverseRepurchaseAgreementsNarrativeDetails">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AssetsSoldUnderAgreementsToRepurchaseLineItems_0c83a06b-710a-438a-aad5-6c1ed42b6cfc" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AssetsSoldUnderAgreementsToRepurchaseLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_ReceivableUnderReverseRepurchaseAgreements_ca36cc36-f745-41b8-83f1-0428e3359e65" xlink:href="agnc-20220331.xsd#agnc_ReceivableUnderReverseRepurchaseAgreements"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AssetsSoldUnderAgreementsToRepurchaseLineItems_0c83a06b-710a-438a-aad5-6c1ed42b6cfc" xlink:to="loc_agnc_ReceivableUnderReverseRepurchaseAgreements_ca36cc36-f745-41b8-83f1-0428e3359e65" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SecuritiesSoldUnderAgreementsToRepurchase_1fd810f2-5917-4a58-b571-edfa553aca0a" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_SecuritiesSoldUnderAgreementsToRepurchase"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AssetsSoldUnderAgreementsToRepurchaseLineItems_0c83a06b-710a-438a-aad5-6c1ed42b6cfc" xlink:to="loc_us-gaap_SecuritiesSoldUnderAgreementsToRepurchase_1fd810f2-5917-4a58-b571-edfa553aca0a" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_DerivativeForwardSettlementValue_17801b14-8c1e-42c3-98a6-c8c6c4d269c9" xlink:href="agnc-20220331.xsd#agnc_DerivativeForwardSettlementValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AssetsSoldUnderAgreementsToRepurchaseLineItems_0c83a06b-710a-438a-aad5-6c1ed42b6cfc" xlink:to="loc_agnc_DerivativeForwardSettlementValue_17801b14-8c1e-42c3-98a6-c8c6c4d269c9" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DerivativeFairValueOfDerivativeNet_93e22f3c-5d97-4d82-a575-6ce0270c1bb2" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DerivativeFairValueOfDerivativeNet"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AssetsSoldUnderAgreementsToRepurchaseLineItems_0c83a06b-710a-438a-aad5-6c1ed42b6cfc" xlink:to="loc_us-gaap_DerivativeFairValueOfDerivativeNet_93e22f3c-5d97-4d82-a575-6ce0270c1bb2" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_PercentageofRepurchaseAgreementFunding_04bf34d7-ad1d-4aba-b2fa-30e420189e35" xlink:href="agnc-20220331.xsd#agnc_PercentageofRepurchaseAgreementFunding"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AssetsSoldUnderAgreementsToRepurchaseLineItems_0c83a06b-710a-438a-aad5-6c1ed42b6cfc" xlink:to="loc_agnc_PercentageofRepurchaseAgreementFunding_04bf34d7-ad1d-4aba-b2fa-30e420189e35" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_ObligationToReturnSecuritiesBorrowedUnderReverseRepurchaseAgreementsAtFairValue_6a4e7c77-f5f5-4f7d-a9e5-efe8a1e4a6f7" xlink:href="agnc-20220331.xsd#agnc_ObligationToReturnSecuritiesBorrowedUnderReverseRepurchaseAgreementsAtFairValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AssetsSoldUnderAgreementsToRepurchaseLineItems_0c83a06b-710a-438a-aad5-6c1ed42b6cfc" xlink:to="loc_agnc_ObligationToReturnSecuritiesBorrowedUnderReverseRepurchaseAgreementsAtFairValue_6a4e7c77-f5f5-4f7d-a9e5-efe8a1e4a6f7" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_WeightedAverageForwardStartDate_e2bb3ad2-0226-4f6f-ae10-b697136cb1a4" xlink:href="agnc-20220331.xsd#agnc_WeightedAverageForwardStartDate"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AssetsSoldUnderAgreementsToRepurchaseLineItems_0c83a06b-710a-438a-aad5-6c1ed42b6cfc" xlink:to="loc_agnc_WeightedAverageForwardStartDate_e2bb3ad2-0226-4f6f-ae10-b697136cb1a4" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_WeightedAverageForwardStartDays_5a53ede2-d28a-4703-809d-30373986709e" xlink:href="agnc-20220331.xsd#agnc_WeightedAverageForwardStartDays"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AssetsSoldUnderAgreementsToRepurchaseLineItems_0c83a06b-710a-438a-aad5-6c1ed42b6cfc" xlink:to="loc_agnc_WeightedAverageForwardStartDays_5a53ede2-d28a-4703-809d-30373986709e" xlink:type="arc" order="7"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShortTermDebtWeightedAverageInterestRate_37da193e-31ce-466b-9f94-38e18d5a9f2d" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShortTermDebtWeightedAverageInterestRate"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AssetsSoldUnderAgreementsToRepurchaseLineItems_0c83a06b-710a-438a-aad5-6c1ed42b6cfc" xlink:to="loc_us-gaap_ShortTermDebtWeightedAverageInterestRate_37da193e-31ce-466b-9f94-38e18d5a9f2d" xlink:type="arc" order="8"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherLongTermDebt_f3b482e9-3506-4f9d-bc4b-52e7cb827235" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_OtherLongTermDebt"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AssetsSoldUnderAgreementsToRepurchaseLineItems_0c83a06b-710a-438a-aad5-6c1ed42b6cfc" xlink:to="loc_us-gaap_OtherLongTermDebt_f3b482e9-3506-4f9d-bc4b-52e7cb827235" xlink:type="arc" order="9"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentDescriptionOfVariableRateBasis_337bb7ba-be4e-4ccd-894d-b670aac51cb1" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DebtInstrumentDescriptionOfVariableRateBasis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AssetsSoldUnderAgreementsToRepurchaseLineItems_0c83a06b-710a-438a-aad5-6c1ed42b6cfc" xlink:to="loc_us-gaap_DebtInstrumentDescriptionOfVariableRateBasis_337bb7ba-be4e-4ccd-894d-b670aac51cb1" xlink:type="arc" order="10"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_SpreadOverLibor_2b805e17-bee8-4014-8825-8639cf36b7e6" xlink:href="agnc-20220331.xsd#agnc_SpreadOverLibor"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AssetsSoldUnderAgreementsToRepurchaseLineItems_0c83a06b-710a-438a-aad5-6c1ed42b6cfc" xlink:to="loc_agnc_SpreadOverLibor_2b805e17-bee8-4014-8825-8639cf36b7e6" xlink:type="arc" order="11"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentFaceAmount_1f267f5c-3c03-49e9-9c28-5c03cf146794" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DebtInstrumentFaceAmount"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AssetsSoldUnderAgreementsToRepurchaseLineItems_0c83a06b-710a-438a-aad5-6c1ed42b6cfc" xlink:to="loc_us-gaap_DebtInstrumentFaceAmount_1f267f5c-3c03-49e9-9c28-5c03cf146794" xlink:type="arc" order="12"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_WeightedAverageLifeOtherDebt_593e16fe-acda-425b-8609-e0c75ee32e81" xlink:href="agnc-20220331.xsd#agnc_WeightedAverageLifeOtherDebt"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AssetsSoldUnderAgreementsToRepurchaseLineItems_0c83a06b-710a-438a-aad5-6c1ed42b6cfc" xlink:to="loc_agnc_WeightedAverageLifeOtherDebt_593e16fe-acda-425b-8609-e0c75ee32e81" xlink:type="arc" order="13"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_RepurchaseAgreementsExtinguishedExtinguishmentOfDebt_0c9eae09-4e2a-4f1e-9b4d-aaf8505227cd" xlink:href="agnc-20220331.xsd#agnc_RepurchaseAgreementsExtinguishedExtinguishmentOfDebt"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AssetsSoldUnderAgreementsToRepurchaseLineItems_0c83a06b-710a-438a-aad5-6c1ed42b6cfc" xlink:to="loc_agnc_RepurchaseAgreementsExtinguishedExtinguishmentOfDebt_0c9eae09-4e2a-4f1e-9b4d-aaf8505227cd" xlink:type="arc" order="14"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_WeightedAverageRemainingMaturityOfRepurchaseAgreementsExtinguishedExtinguishedDebt_e953558c-df0a-4c8c-a7c6-8f9f9d62eef7" xlink:href="agnc-20220331.xsd#agnc_WeightedAverageRemainingMaturityOfRepurchaseAgreementsExtinguishedExtinguishedDebt"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AssetsSoldUnderAgreementsToRepurchaseLineItems_0c83a06b-710a-438a-aad5-6c1ed42b6cfc" xlink:to="loc_agnc_WeightedAverageRemainingMaturityOfRepurchaseAgreementsExtinguishedExtinguishedDebt_e953558c-df0a-4c8c-a7c6-8f9f9d62eef7" xlink:type="arc" order="15"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_GainsLossesOnExtinguishmentOfDebt_ae892250-28e5-4af1-9775-8ae40524c80c" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_GainsLossesOnExtinguishmentOfDebt"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AssetsSoldUnderAgreementsToRepurchaseLineItems_0c83a06b-710a-438a-aad5-6c1ed42b6cfc" xlink:to="loc_us-gaap_GainsLossesOnExtinguishmentOfDebt_ae892250-28e5-4af1-9775-8ae40524c80c" xlink:type="arc" order="16"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_WeightedAverageInterestRateOfRepurchaseAgreementsExtinguishedExtinguishedDebt_7981020e-6b39-4e4b-93a8-67e3537e71c8" xlink:href="agnc-20220331.xsd#agnc_WeightedAverageInterestRateOfRepurchaseAgreementsExtinguishedExtinguishedDebt"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AssetsSoldUnderAgreementsToRepurchaseLineItems_0c83a06b-710a-438a-aad5-6c1ed42b6cfc" xlink:to="loc_agnc_WeightedAverageInterestRateOfRepurchaseAgreementsExtinguishedExtinguishedDebt_7981020e-6b39-4e4b-93a8-67e3537e71c8" xlink:type="arc" order="17"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShortTermDebtWeightedAverageInterestRateOverTime_e67ecd27-63fa-4315-92db-920ea59e931c" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShortTermDebtWeightedAverageInterestRateOverTime"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AssetsSoldUnderAgreementsToRepurchaseLineItems_0c83a06b-710a-438a-aad5-6c1ed42b6cfc" xlink:to="loc_us-gaap_ShortTermDebtWeightedAverageInterestRateOverTime_e67ecd27-63fa-4315-92db-920ea59e931c" xlink:type="arc" order="18"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfAssetsSoldUnderAgreementsToRepurchaseTable_fb0d8de6-6d57-45d9-a837-84951298a2b2" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ScheduleOfAssetsSoldUnderAgreementsToRepurchaseTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_AssetsSoldUnderAgreementsToRepurchaseLineItems_0c83a06b-710a-438a-aad5-6c1ed42b6cfc" xlink:to="loc_us-gaap_ScheduleOfAssetsSoldUnderAgreementsToRepurchaseTable_fb0d8de6-6d57-45d9-a837-84951298a2b2" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_CounterpartyNameAxis_50dce06b-bf69-410b-9307-80fdf60a1947" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_CounterpartyNameAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfAssetsSoldUnderAgreementsToRepurchaseTable_fb0d8de6-6d57-45d9-a837-84951298a2b2" xlink:to="loc_srt_CounterpartyNameAxis_50dce06b-bf69-410b-9307-80fdf60a1947" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RepurchaseAgreementCounterpartyNameDomain_50dce06b-bf69-410b-9307-80fdf60a1947_default" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_RepurchaseAgreementCounterpartyNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_CounterpartyNameAxis_50dce06b-bf69-410b-9307-80fdf60a1947" xlink:to="loc_srt_RepurchaseAgreementCounterpartyNameDomain_50dce06b-bf69-410b-9307-80fdf60a1947_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RepurchaseAgreementCounterpartyNameDomain_ef82937b-b872-4eec-a4c4-461804366865" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_RepurchaseAgreementCounterpartyNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_CounterpartyNameAxis_50dce06b-bf69-410b-9307-80fdf60a1947" xlink:to="loc_srt_RepurchaseAgreementCounterpartyNameDomain_ef82937b-b872-4eec-a4c4-461804366865" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_BethesdaSecuritiesMember_0de4406b-1cc3-41a5-96a8-af2e3a845a54" xlink:href="agnc-20220331.xsd#agnc_BethesdaSecuritiesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RepurchaseAgreementCounterpartyNameDomain_ef82937b-b872-4eec-a4c4-461804366865" xlink:to="loc_agnc_BethesdaSecuritiesMember_0de4406b-1cc3-41a5-96a8-af2e3a845a54" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_FICCMember_dcaeb0a8-ebf2-49d4-b487-6b8d61d62d25" xlink:href="agnc-20220331.xsd#agnc_FICCMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RepurchaseAgreementCounterpartyNameDomain_ef82937b-b872-4eec-a4c4-461804366865" xlink:to="loc_agnc_FICCMember_dcaeb0a8-ebf2-49d4-b487-6b8d61d62d25" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FinancialInstrumentAxis_79e7e445-d6d6-448e-9e6c-61e4724c49b9" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FinancialInstrumentAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfAssetsSoldUnderAgreementsToRepurchaseTable_fb0d8de6-6d57-45d9-a837-84951298a2b2" xlink:to="loc_us-gaap_FinancialInstrumentAxis_79e7e445-d6d6-448e-9e6c-61e4724c49b9" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_79e7e445-d6d6-448e-9e6c-61e4724c49b9_default" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_FinancialInstrumentAxis_79e7e445-d6d6-448e-9e6c-61e4724c49b9" xlink:to="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_79e7e445-d6d6-448e-9e6c-61e4724c49b9_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_4bea7c57-5d90-4aa7-9d8d-a54bb07982c6" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_FinancialInstrumentAxis_79e7e445-d6d6-448e-9e6c-61e4724c49b9" xlink:to="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_4bea7c57-5d90-4aa7-9d8d-a54bb07982c6" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_USTreasurySecuritiesMember_c6aea83d-6cee-4e0f-97b3-87e322ef6a84" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_USTreasurySecuritiesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_4bea7c57-5d90-4aa7-9d8d-a54bb07982c6" xlink:to="loc_us-gaap_USTreasurySecuritiesMember_c6aea83d-6cee-4e0f-97b3-87e322ef6a84" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AssetsSoldUnderAgreementsToRepurchaseMaturityPeriodsAxis_5ae00694-3438-4e5c-8263-86c545fe4cee" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AssetsSoldUnderAgreementsToRepurchaseMaturityPeriodsAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfAssetsSoldUnderAgreementsToRepurchaseTable_fb0d8de6-6d57-45d9-a837-84951298a2b2" xlink:to="loc_us-gaap_AssetsSoldUnderAgreementsToRepurchaseMaturityPeriodsAxis_5ae00694-3438-4e5c-8263-86c545fe4cee" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AssetsSoldUnderAgreementsToRepurchaseMaturityPeriodDomain_5ae00694-3438-4e5c-8263-86c545fe4cee_default" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AssetsSoldUnderAgreementsToRepurchaseMaturityPeriodDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_AssetsSoldUnderAgreementsToRepurchaseMaturityPeriodsAxis_5ae00694-3438-4e5c-8263-86c545fe4cee" xlink:to="loc_us-gaap_AssetsSoldUnderAgreementsToRepurchaseMaturityPeriodDomain_5ae00694-3438-4e5c-8263-86c545fe4cee_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AssetsSoldUnderAgreementsToRepurchaseMaturityPeriodDomain_b1141ae8-cf5d-4fd0-a066-91db7d965005" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AssetsSoldUnderAgreementsToRepurchaseMaturityPeriodDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_AssetsSoldUnderAgreementsToRepurchaseMaturityPeriodsAxis_5ae00694-3438-4e5c-8263-86c545fe4cee" xlink:to="loc_us-gaap_AssetsSoldUnderAgreementsToRepurchaseMaturityPeriodDomain_b1141ae8-cf5d-4fd0-a066-91db7d965005" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_MaturityOvernightMember_637cc500-ae3f-44a6-8ae8-47dfc8cf0292" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_MaturityOvernightMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AssetsSoldUnderAgreementsToRepurchaseMaturityPeriodDomain_b1141ae8-cf5d-4fd0-a066-91db7d965005" xlink:to="loc_us-gaap_MaturityOvernightMember_637cc500-ae3f-44a6-8ae8-47dfc8cf0292" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ForwardContractsMember_9f0f842c-5a5a-43e7-9cf3-27bde78352a9" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ForwardContractsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AssetsSoldUnderAgreementsToRepurchaseMaturityPeriodDomain_b1141ae8-cf5d-4fd0-a066-91db7d965005" xlink:to="loc_us-gaap_ForwardContractsMember_9f0f842c-5a5a-43e7-9cf3-27bde78352a9" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DerivativeInstrumentRiskAxis_a33ec8c0-8a9f-400f-8a37-05f4824d01f1" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DerivativeInstrumentRiskAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfAssetsSoldUnderAgreementsToRepurchaseTable_fb0d8de6-6d57-45d9-a837-84951298a2b2" xlink:to="loc_us-gaap_DerivativeInstrumentRiskAxis_a33ec8c0-8a9f-400f-8a37-05f4824d01f1" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DerivativeContractTypeDomain_a33ec8c0-8a9f-400f-8a37-05f4824d01f1_default" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DerivativeContractTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_DerivativeInstrumentRiskAxis_a33ec8c0-8a9f-400f-8a37-05f4824d01f1" xlink:to="loc_us-gaap_DerivativeContractTypeDomain_a33ec8c0-8a9f-400f-8a37-05f4824d01f1_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DerivativeContractTypeDomain_caf6d213-fc3b-4cdb-b404-21d535ef139b" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DerivativeContractTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_DerivativeInstrumentRiskAxis_a33ec8c0-8a9f-400f-8a37-05f4824d01f1" xlink:to="loc_us-gaap_DerivativeContractTypeDomain_caf6d213-fc3b-4cdb-b404-21d535ef139b" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_TbaSecuritiesFifteenYearAndThirtyYearSecuritiesMember_220a254d-a95d-4176-9b27-7419bd0ac9f9" xlink:href="agnc-20220331.xsd#agnc_TbaSecuritiesFifteenYearAndThirtyYearSecuritiesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DerivativeContractTypeDomain_caf6d213-fc3b-4cdb-b404-21d535ef139b" xlink:to="loc_agnc_TbaSecuritiesFifteenYearAndThirtyYearSecuritiesMember_220a254d-a95d-4176-9b27-7419bd0ac9f9" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_TBAAndForwardSettlingSecuritiesMember_97c13d13-0c49-48c0-8477-910e91fd7718" xlink:href="agnc-20220331.xsd#agnc_TBAAndForwardSettlingSecuritiesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DerivativeContractTypeDomain_caf6d213-fc3b-4cdb-b404-21d535ef139b" xlink:to="loc_agnc_TBAAndForwardSettlingSecuritiesMember_97c13d13-0c49-48c0-8477-910e91fd7718" xlink:type="arc" order="1"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.agnc.com/role/RepurchaseAgreementsAndOtherDebtRepurchaseArrangementsAndWeightedAverageInterestRatesClassifiedByOriginalMaturitiesDetails" xlink:type="simple" xlink:href="agnc-20220331.xsd#RepurchaseAgreementsAndOtherDebtRepurchaseArrangementsAndWeightedAverageInterestRatesClassifiedByOriginalMaturitiesDetails"/>
  <link:definitionLink xlink:role="http://www.agnc.com/role/RepurchaseAgreementsAndOtherDebtRepurchaseArrangementsAndWeightedAverageInterestRatesClassifiedByOriginalMaturitiesDetails" xlink:type="extended" id="i0ed73a67c6e34cec90330834e21d19f6_RepurchaseAgreementsAndOtherDebtRepurchaseArrangementsAndWeightedAverageInterestRatesClassifiedByOriginalMaturitiesDetails">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StatementLineItems_168fefa0-c4d4-42aa-9e23-5563b135f61b" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_StatementLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_ReceivableUnderReverseRepurchaseAgreements_d7c09848-5651-4969-9fcb-b106438f5a4e" xlink:href="agnc-20220331.xsd#agnc_ReceivableUnderReverseRepurchaseAgreements"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_168fefa0-c4d4-42aa-9e23-5563b135f61b" xlink:to="loc_agnc_ReceivableUnderReverseRepurchaseAgreements_d7c09848-5651-4969-9fcb-b106438f5a4e" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SecuritiesSoldUnderAgreementsToRepurchase_b151ea5e-c82a-44bc-97ef-e116d1321a51" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_SecuritiesSoldUnderAgreementsToRepurchase"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_168fefa0-c4d4-42aa-9e23-5563b135f61b" xlink:to="loc_us-gaap_SecuritiesSoldUnderAgreementsToRepurchase_b151ea5e-c82a-44bc-97ef-e116d1321a51" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShortTermDebtWeightedAverageInterestRate_a87b5e7a-041c-44bf-a2fd-592043c2d59b" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShortTermDebtWeightedAverageInterestRate"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_168fefa0-c4d4-42aa-9e23-5563b135f61b" xlink:to="loc_us-gaap_ShortTermDebtWeightedAverageInterestRate_a87b5e7a-041c-44bf-a2fd-592043c2d59b" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_RepurchaseAgreementsWeightedAverageDaysToMaturity_a5b81ff7-4fa3-464a-a7e3-28cd4690db46" xlink:href="agnc-20220331.xsd#agnc_RepurchaseAgreementsWeightedAverageDaysToMaturity"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_168fefa0-c4d4-42aa-9e23-5563b135f61b" xlink:to="loc_agnc_RepurchaseAgreementsWeightedAverageDaysToMaturity_a5b81ff7-4fa3-464a-a7e3-28cd4690db46" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_ObligationToReturnSecuritiesBorrowedUnderReverseRepurchaseAgreementsAtFairValue_8793b890-033a-49ba-8676-3d4d0e822e79" xlink:href="agnc-20220331.xsd#agnc_ObligationToReturnSecuritiesBorrowedUnderReverseRepurchaseAgreementsAtFairValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_168fefa0-c4d4-42aa-9e23-5563b135f61b" xlink:to="loc_agnc_ObligationToReturnSecuritiesBorrowedUnderReverseRepurchaseAgreementsAtFairValue_8793b890-033a-49ba-8676-3d4d0e822e79" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfAssetsSoldUnderAgreementsToRepurchaseTable_468312ac-efc3-4d34-b59e-57fedd7796ef" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ScheduleOfAssetsSoldUnderAgreementsToRepurchaseTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_StatementLineItems_168fefa0-c4d4-42aa-9e23-5563b135f61b" xlink:to="loc_us-gaap_ScheduleOfAssetsSoldUnderAgreementsToRepurchaseTable_468312ac-efc3-4d34-b59e-57fedd7796ef" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AssetsSoldUnderAgreementsToRepurchaseAxis_e6bbb891-2498-418f-8465-f2155b166881" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AssetsSoldUnderAgreementsToRepurchaseAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfAssetsSoldUnderAgreementsToRepurchaseTable_468312ac-efc3-4d34-b59e-57fedd7796ef" xlink:to="loc_us-gaap_AssetsSoldUnderAgreementsToRepurchaseAxis_e6bbb891-2498-418f-8465-f2155b166881" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AssetsSoldUnderAgreementsToRepurchaseTypeDomain_e6bbb891-2498-418f-8465-f2155b166881_default" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AssetsSoldUnderAgreementsToRepurchaseTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_AssetsSoldUnderAgreementsToRepurchaseAxis_e6bbb891-2498-418f-8465-f2155b166881" xlink:to="loc_us-gaap_AssetsSoldUnderAgreementsToRepurchaseTypeDomain_e6bbb891-2498-418f-8465-f2155b166881_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AssetsSoldUnderAgreementsToRepurchaseTypeDomain_188b88df-a7ce-46cf-a89a-03d91fdfcdaa" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AssetsSoldUnderAgreementsToRepurchaseTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_AssetsSoldUnderAgreementsToRepurchaseAxis_e6bbb891-2498-418f-8465-f2155b166881" xlink:to="loc_us-gaap_AssetsSoldUnderAgreementsToRepurchaseTypeDomain_188b88df-a7ce-46cf-a89a-03d91fdfcdaa" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_USGovernmentAgenciesDebtSecuritiesMember_77732aaf-6ba6-4fa5-9018-f9e639f276fe" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_USGovernmentAgenciesDebtSecuritiesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AssetsSoldUnderAgreementsToRepurchaseTypeDomain_188b88df-a7ce-46cf-a89a-03d91fdfcdaa" xlink:to="loc_us-gaap_USGovernmentAgenciesDebtSecuritiesMember_77732aaf-6ba6-4fa5-9018-f9e639f276fe" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_CounterpartyNameAxis_09e959b7-40e0-4226-a3bd-12fb31fe14f1" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_CounterpartyNameAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfAssetsSoldUnderAgreementsToRepurchaseTable_468312ac-efc3-4d34-b59e-57fedd7796ef" xlink:to="loc_srt_CounterpartyNameAxis_09e959b7-40e0-4226-a3bd-12fb31fe14f1" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RepurchaseAgreementCounterpartyNameDomain_09e959b7-40e0-4226-a3bd-12fb31fe14f1_default" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_RepurchaseAgreementCounterpartyNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_CounterpartyNameAxis_09e959b7-40e0-4226-a3bd-12fb31fe14f1" xlink:to="loc_srt_RepurchaseAgreementCounterpartyNameDomain_09e959b7-40e0-4226-a3bd-12fb31fe14f1_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RepurchaseAgreementCounterpartyNameDomain_f5d7cc1d-07ab-4f6e-8eb5-62203b38a934" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_RepurchaseAgreementCounterpartyNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_CounterpartyNameAxis_09e959b7-40e0-4226-a3bd-12fb31fe14f1" xlink:to="loc_srt_RepurchaseAgreementCounterpartyNameDomain_f5d7cc1d-07ab-4f6e-8eb5-62203b38a934" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_FICCMember_fd5263f4-09d2-4762-abe8-57500072b9a3" xlink:href="agnc-20220331.xsd#agnc_FICCMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RepurchaseAgreementCounterpartyNameDomain_f5d7cc1d-07ab-4f6e-8eb5-62203b38a934" xlink:to="loc_agnc_FICCMember_fd5263f4-09d2-4762-abe8-57500072b9a3" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FinancialInstrumentAxis_74b3fc15-f47f-431b-808f-3a40ed69eac7" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FinancialInstrumentAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfAssetsSoldUnderAgreementsToRepurchaseTable_468312ac-efc3-4d34-b59e-57fedd7796ef" xlink:to="loc_us-gaap_FinancialInstrumentAxis_74b3fc15-f47f-431b-808f-3a40ed69eac7" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_74b3fc15-f47f-431b-808f-3a40ed69eac7_default" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_FinancialInstrumentAxis_74b3fc15-f47f-431b-808f-3a40ed69eac7" xlink:to="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_74b3fc15-f47f-431b-808f-3a40ed69eac7_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_001c16d2-6ec5-4b50-bbe9-36e5ff4055d2" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_FinancialInstrumentAxis_74b3fc15-f47f-431b-808f-3a40ed69eac7" xlink:to="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_001c16d2-6ec5-4b50-bbe9-36e5ff4055d2" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_USTreasurySecuritiesMember_8f7a0c0b-3c95-4eff-ad3d-bf199e905eed" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_USTreasurySecuritiesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_001c16d2-6ec5-4b50-bbe9-36e5ff4055d2" xlink:to="loc_us-gaap_USTreasurySecuritiesMember_8f7a0c0b-3c95-4eff-ad3d-bf199e905eed" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentAxis_aae99058-40ca-4b44-a85c-4f6a6de424f9" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DebtInstrumentAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfAssetsSoldUnderAgreementsToRepurchaseTable_468312ac-efc3-4d34-b59e-57fedd7796ef" xlink:to="loc_us-gaap_DebtInstrumentAxis_aae99058-40ca-4b44-a85c-4f6a6de424f9" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentNameDomain_aae99058-40ca-4b44-a85c-4f6a6de424f9_default" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DebtInstrumentNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_DebtInstrumentAxis_aae99058-40ca-4b44-a85c-4f6a6de424f9" xlink:to="loc_us-gaap_DebtInstrumentNameDomain_aae99058-40ca-4b44-a85c-4f6a6de424f9_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentNameDomain_1b7cb38a-3a86-4191-bf33-66d4b2335053" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DebtInstrumentNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_DebtInstrumentAxis_aae99058-40ca-4b44-a85c-4f6a6de424f9" xlink:to="loc_us-gaap_DebtInstrumentNameDomain_1b7cb38a-3a86-4191-bf33-66d4b2335053" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RepurchaseAgreementsMember_cef04e89-c38d-4ede-8335-428012cd83e6" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_RepurchaseAgreementsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentNameDomain_1b7cb38a-3a86-4191-bf33-66d4b2335053" xlink:to="loc_us-gaap_RepurchaseAgreementsMember_cef04e89-c38d-4ede-8335-428012cd83e6" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_USTreasurySecuritiesMember_c195fd60-3c21-43de-9f20-82f5bbc6fcfe" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_USTreasurySecuritiesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentNameDomain_1b7cb38a-3a86-4191-bf33-66d4b2335053" xlink:to="loc_us-gaap_USTreasurySecuritiesMember_c195fd60-3c21-43de-9f20-82f5bbc6fcfe" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AssetsSoldUnderAgreementsToRepurchaseMaturityPeriodsAxis_8be39fa2-407d-4e20-98d3-17afbd6c939e" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AssetsSoldUnderAgreementsToRepurchaseMaturityPeriodsAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfAssetsSoldUnderAgreementsToRepurchaseTable_468312ac-efc3-4d34-b59e-57fedd7796ef" xlink:to="loc_us-gaap_AssetsSoldUnderAgreementsToRepurchaseMaturityPeriodsAxis_8be39fa2-407d-4e20-98d3-17afbd6c939e" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AssetsSoldUnderAgreementsToRepurchaseMaturityPeriodDomain_8be39fa2-407d-4e20-98d3-17afbd6c939e_default" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AssetsSoldUnderAgreementsToRepurchaseMaturityPeriodDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_AssetsSoldUnderAgreementsToRepurchaseMaturityPeriodsAxis_8be39fa2-407d-4e20-98d3-17afbd6c939e" xlink:to="loc_us-gaap_AssetsSoldUnderAgreementsToRepurchaseMaturityPeriodDomain_8be39fa2-407d-4e20-98d3-17afbd6c939e_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AssetsSoldUnderAgreementsToRepurchaseMaturityPeriodDomain_da37dd6f-d228-4f1c-8a36-79fc96b1d09e" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AssetsSoldUnderAgreementsToRepurchaseMaturityPeriodDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_AssetsSoldUnderAgreementsToRepurchaseMaturityPeriodsAxis_8be39fa2-407d-4e20-98d3-17afbd6c939e" xlink:to="loc_us-gaap_AssetsSoldUnderAgreementsToRepurchaseMaturityPeriodDomain_da37dd6f-d228-4f1c-8a36-79fc96b1d09e" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_MaturityOvernightMember_7b0d090e-4804-4461-bedb-0bd89a4fa6f5" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_MaturityOvernightMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AssetsSoldUnderAgreementsToRepurchaseMaturityPeriodDomain_da37dd6f-d228-4f1c-8a36-79fc96b1d09e" xlink:to="loc_us-gaap_MaturityOvernightMember_7b0d090e-4804-4461-bedb-0bd89a4fa6f5" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_MaturityUpTo30DaysMember_d496fc9d-5abf-40ea-9411-8987e2b4965a" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_MaturityUpTo30DaysMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AssetsSoldUnderAgreementsToRepurchaseMaturityPeriodDomain_da37dd6f-d228-4f1c-8a36-79fc96b1d09e" xlink:to="loc_us-gaap_MaturityUpTo30DaysMember_d496fc9d-5abf-40ea-9411-8987e2b4965a" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_ThirtyOneToNinetyMember_5ceff433-6aea-4441-bf6e-d4fce204b756" xlink:href="agnc-20220331.xsd#agnc_ThirtyOneToNinetyMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AssetsSoldUnderAgreementsToRepurchaseMaturityPeriodDomain_da37dd6f-d228-4f1c-8a36-79fc96b1d09e" xlink:to="loc_agnc_ThirtyOneToNinetyMember_5ceff433-6aea-4441-bf6e-d4fce204b756" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_A4to6MonthsMember_8f638306-8959-41cd-804d-a6b90b534670" xlink:href="agnc-20220331.xsd#agnc_A4to6MonthsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AssetsSoldUnderAgreementsToRepurchaseMaturityPeriodDomain_da37dd6f-d228-4f1c-8a36-79fc96b1d09e" xlink:to="loc_agnc_A4to6MonthsMember_8f638306-8959-41cd-804d-a6b90b534670" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_A7to9monthsMember_d2d80a77-5103-4a26-b2c5-bb447d61b4bf" xlink:href="agnc-20220331.xsd#agnc_A7to9monthsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AssetsSoldUnderAgreementsToRepurchaseMaturityPeriodDomain_da37dd6f-d228-4f1c-8a36-79fc96b1d09e" xlink:to="loc_agnc_A7to9monthsMember_d2d80a77-5103-4a26-b2c5-bb447d61b4bf" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_A10to12MonthsMember_ed1339d0-2606-4930-9cac-dc75ed9f09ed" xlink:href="agnc-20220331.xsd#agnc_A10to12MonthsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AssetsSoldUnderAgreementsToRepurchaseMaturityPeriodDomain_da37dd6f-d228-4f1c-8a36-79fc96b1d09e" xlink:to="loc_agnc_A10to12MonthsMember_ed1339d0-2606-4930-9cac-dc75ed9f09ed" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_A13to24MonthsMember_b0168d11-38ee-4fd7-b7bc-0a49facc6c66" xlink:href="agnc-20220331.xsd#agnc_A13to24MonthsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AssetsSoldUnderAgreementsToRepurchaseMaturityPeriodDomain_da37dd6f-d228-4f1c-8a36-79fc96b1d09e" xlink:to="loc_agnc_A13to24MonthsMember_b0168d11-38ee-4fd7-b7bc-0a49facc6c66" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_A25to36monthsMember_e2764c42-35de-4c08-b91f-112da74805cf" xlink:href="agnc-20220331.xsd#agnc_A25to36monthsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AssetsSoldUnderAgreementsToRepurchaseMaturityPeriodDomain_da37dd6f-d228-4f1c-8a36-79fc96b1d09e" xlink:to="loc_agnc_A25to36monthsMember_e2764c42-35de-4c08-b91f-112da74805cf" xlink:type="arc" order="7"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_A37to48monthsMember_696dc84d-3e3d-4139-8f8d-cff48fd30b87" xlink:href="agnc-20220331.xsd#agnc_A37to48monthsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AssetsSoldUnderAgreementsToRepurchaseMaturityPeriodDomain_da37dd6f-d228-4f1c-8a36-79fc96b1d09e" xlink:to="loc_agnc_A37to48monthsMember_696dc84d-3e3d-4139-8f8d-cff48fd30b87" xlink:type="arc" order="8"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_A49to60MonthsMember_93fb66a0-2d25-45ba-8b47-cfbebb858cad" xlink:href="agnc-20220331.xsd#agnc_A49to60MonthsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AssetsSoldUnderAgreementsToRepurchaseMaturityPeriodDomain_da37dd6f-d228-4f1c-8a36-79fc96b1d09e" xlink:to="loc_agnc_A49to60MonthsMember_93fb66a0-2d25-45ba-8b47-cfbebb858cad" xlink:type="arc" order="9"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_A2Daysto1MonthMember_e0d7c037-f077-4e5e-a55b-775022d8e6ba" xlink:href="agnc-20220331.xsd#agnc_A2Daysto1MonthMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AssetsSoldUnderAgreementsToRepurchaseMaturityPeriodDomain_da37dd6f-d228-4f1c-8a36-79fc96b1d09e" xlink:to="loc_agnc_A2Daysto1MonthMember_e0d7c037-f077-4e5e-a55b-775022d8e6ba" xlink:type="arc" order="10"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.agnc.com/role/RepurchaseAgreementsAndReverseRepurchaseAgreementsFederalHomeLoanBankAdvancesandWeightedAverageInterestRatesDetails" xlink:type="simple" xlink:href="agnc-20220331.xsd#RepurchaseAgreementsAndReverseRepurchaseAgreementsFederalHomeLoanBankAdvancesandWeightedAverageInterestRatesDetails"/>
  <link:definitionLink xlink:role="http://www.agnc.com/role/RepurchaseAgreementsAndReverseRepurchaseAgreementsFederalHomeLoanBankAdvancesandWeightedAverageInterestRatesDetails" xlink:type="extended" id="ib1ce982ccc0d4a508e0376239c85655f_RepurchaseAgreementsAndReverseRepurchaseAgreementsFederalHomeLoanBankAdvancesandWeightedAverageInterestRatesDetails">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShortTermDebtLineItems_2ff7fe03-bcd2-48ce-b3af-30956230c598" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShortTermDebtLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShortTermDebtPercentageBearingFixedInterestRate_04b89241-2230-4343-9004-0723fd3d97b1" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShortTermDebtPercentageBearingFixedInterestRate"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShortTermDebtLineItems_2ff7fe03-bcd2-48ce-b3af-30956230c598" xlink:to="loc_us-gaap_ShortTermDebtPercentageBearingFixedInterestRate_04b89241-2230-4343-9004-0723fd3d97b1" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AdvancesFromFederalHomeLoanBanks_97276aec-6c25-482b-b4f0-225290f30c9e" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AdvancesFromFederalHomeLoanBanks"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShortTermDebtLineItems_2ff7fe03-bcd2-48ce-b3af-30956230c598" xlink:to="loc_us-gaap_AdvancesFromFederalHomeLoanBanks_97276aec-6c25-482b-b4f0-225290f30c9e" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfShortTermDebtTable_3b294dc9-278a-48a8-99e5-f7e57da4ecd6" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ScheduleOfShortTermDebtTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_ShortTermDebtLineItems_2ff7fe03-bcd2-48ce-b3af-30956230c598" xlink:to="loc_us-gaap_ScheduleOfShortTermDebtTable_3b294dc9-278a-48a8-99e5-f7e57da4ecd6" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeAxis_bab2bdce-1f15-4f32-8b59-1fafce71c481" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_RangeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfShortTermDebtTable_3b294dc9-278a-48a8-99e5-f7e57da4ecd6" xlink:to="loc_srt_RangeAxis_bab2bdce-1f15-4f32-8b59-1fafce71c481" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeMember_bab2bdce-1f15-4f32-8b59-1fafce71c481_default" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_RangeMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_RangeAxis_bab2bdce-1f15-4f32-8b59-1fafce71c481" xlink:to="loc_srt_RangeMember_bab2bdce-1f15-4f32-8b59-1fafce71c481_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeMember_73a47f51-aee1-4570-93dd-3c138f5f5d7a" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_RangeMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_RangeAxis_bab2bdce-1f15-4f32-8b59-1fafce71c481" xlink:to="loc_srt_RangeMember_73a47f51-aee1-4570-93dd-3c138f5f5d7a" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AssetsSoldUnderAgreementsToRepurchaseMaturityPeriodsAxis_78785c2f-2d8d-4a11-809d-3dd282d4ad6e" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AssetsSoldUnderAgreementsToRepurchaseMaturityPeriodsAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfShortTermDebtTable_3b294dc9-278a-48a8-99e5-f7e57da4ecd6" xlink:to="loc_us-gaap_AssetsSoldUnderAgreementsToRepurchaseMaturityPeriodsAxis_78785c2f-2d8d-4a11-809d-3dd282d4ad6e" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AssetsSoldUnderAgreementsToRepurchaseMaturityPeriodDomain_78785c2f-2d8d-4a11-809d-3dd282d4ad6e_default" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AssetsSoldUnderAgreementsToRepurchaseMaturityPeriodDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_AssetsSoldUnderAgreementsToRepurchaseMaturityPeriodsAxis_78785c2f-2d8d-4a11-809d-3dd282d4ad6e" xlink:to="loc_us-gaap_AssetsSoldUnderAgreementsToRepurchaseMaturityPeriodDomain_78785c2f-2d8d-4a11-809d-3dd282d4ad6e_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AssetsSoldUnderAgreementsToRepurchaseMaturityPeriodDomain_b18253d0-8cd1-4c1c-9a07-62e7f681c115" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AssetsSoldUnderAgreementsToRepurchaseMaturityPeriodDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_AssetsSoldUnderAgreementsToRepurchaseMaturityPeriodsAxis_78785c2f-2d8d-4a11-809d-3dd282d4ad6e" xlink:to="loc_us-gaap_AssetsSoldUnderAgreementsToRepurchaseMaturityPeriodDomain_b18253d0-8cd1-4c1c-9a07-62e7f681c115" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_A37to48monthsMember_7350db09-5c86-4edb-b499-60804c315333" xlink:href="agnc-20220331.xsd#agnc_A37to48monthsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AssetsSoldUnderAgreementsToRepurchaseMaturityPeriodDomain_b18253d0-8cd1-4c1c-9a07-62e7f681c115" xlink:to="loc_agnc_A37to48monthsMember_7350db09-5c86-4edb-b499-60804c315333" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_FederalHomeLoanBankAdvancesMaturityPeriodAxis_14a4a3ec-276f-4349-8253-02db328f750c" xlink:href="agnc-20220331.xsd#agnc_FederalHomeLoanBankAdvancesMaturityPeriodAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfShortTermDebtTable_3b294dc9-278a-48a8-99e5-f7e57da4ecd6" xlink:to="loc_agnc_FederalHomeLoanBankAdvancesMaturityPeriodAxis_14a4a3ec-276f-4349-8253-02db328f750c" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_FederalHomeLoanBankAdvancesMaturityPeriodDomain_14a4a3ec-276f-4349-8253-02db328f750c_default" xlink:href="agnc-20220331.xsd#agnc_FederalHomeLoanBankAdvancesMaturityPeriodDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_agnc_FederalHomeLoanBankAdvancesMaturityPeriodAxis_14a4a3ec-276f-4349-8253-02db328f750c" xlink:to="loc_agnc_FederalHomeLoanBankAdvancesMaturityPeriodDomain_14a4a3ec-276f-4349-8253-02db328f750c_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_FederalHomeLoanBankAdvancesMaturityPeriodDomain_162e68cb-a5c0-4aad-a81c-75fcb63159c2" xlink:href="agnc-20220331.xsd#agnc_FederalHomeLoanBankAdvancesMaturityPeriodDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_agnc_FederalHomeLoanBankAdvancesMaturityPeriodAxis_14a4a3ec-276f-4349-8253-02db328f750c" xlink:to="loc_agnc_FederalHomeLoanBankAdvancesMaturityPeriodDomain_162e68cb-a5c0-4aad-a81c-75fcb63159c2" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_A49to60MonthsMember_32526fdf-a15a-48f3-ad0c-cb3df724ac6c" xlink:href="agnc-20220331.xsd#agnc_A49to60MonthsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_agnc_FederalHomeLoanBankAdvancesMaturityPeriodDomain_162e68cb-a5c0-4aad-a81c-75fcb63159c2" xlink:to="loc_agnc_A49to60MonthsMember_32526fdf-a15a-48f3-ad0c-cb3df724ac6c" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_A37to48monthsMember_8c8b4419-7ed0-4f96-a290-e1882995297a" xlink:href="agnc-20220331.xsd#agnc_A37to48monthsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_agnc_FederalHomeLoanBankAdvancesMaturityPeriodDomain_162e68cb-a5c0-4aad-a81c-75fcb63159c2" xlink:to="loc_agnc_A37to48monthsMember_8c8b4419-7ed0-4f96-a290-e1882995297a" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_MaturityUpTo30DaysMember_5c314424-dfe3-4de5-a613-831263df10c5" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_MaturityUpTo30DaysMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_agnc_FederalHomeLoanBankAdvancesMaturityPeriodDomain_162e68cb-a5c0-4aad-a81c-75fcb63159c2" xlink:to="loc_us-gaap_MaturityUpTo30DaysMember_5c314424-dfe3-4de5-a613-831263df10c5" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_ThirtyOneToNinetyMember_4f39132d-f74c-4e21-a098-2621c5d72e26" xlink:href="agnc-20220331.xsd#agnc_ThirtyOneToNinetyMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_agnc_FederalHomeLoanBankAdvancesMaturityPeriodDomain_162e68cb-a5c0-4aad-a81c-75fcb63159c2" xlink:to="loc_agnc_ThirtyOneToNinetyMember_4f39132d-f74c-4e21-a098-2621c5d72e26" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_A4to6MonthsMember_e4da82c3-b83a-4468-81c1-4db3b9ffb134" xlink:href="agnc-20220331.xsd#agnc_A4to6MonthsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_agnc_FederalHomeLoanBankAdvancesMaturityPeriodDomain_162e68cb-a5c0-4aad-a81c-75fcb63159c2" xlink:to="loc_agnc_A4to6MonthsMember_e4da82c3-b83a-4468-81c1-4db3b9ffb134" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShortTermDebtTypeAxis_799d6fbc-72f5-4f4b-96be-578497746fbe" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShortTermDebtTypeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfShortTermDebtTable_3b294dc9-278a-48a8-99e5-f7e57da4ecd6" xlink:to="loc_us-gaap_ShortTermDebtTypeAxis_799d6fbc-72f5-4f4b-96be-578497746fbe" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShortTermDebtTypeDomain_799d6fbc-72f5-4f4b-96be-578497746fbe_default" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShortTermDebtTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_ShortTermDebtTypeAxis_799d6fbc-72f5-4f4b-96be-578497746fbe" xlink:to="loc_us-gaap_ShortTermDebtTypeDomain_799d6fbc-72f5-4f4b-96be-578497746fbe_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShortTermDebtTypeDomain_7d254f69-c125-441c-805b-b83833188efd" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShortTermDebtTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_ShortTermDebtTypeAxis_799d6fbc-72f5-4f4b-96be-578497746fbe" xlink:to="loc_us-gaap_ShortTermDebtTypeDomain_7d254f69-c125-441c-805b-b83833188efd" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentAxis_05f12481-6692-40a3-9fd6-94d3d849fa0f" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DebtInstrumentAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfShortTermDebtTable_3b294dc9-278a-48a8-99e5-f7e57da4ecd6" xlink:to="loc_us-gaap_DebtInstrumentAxis_05f12481-6692-40a3-9fd6-94d3d849fa0f" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentNameDomain_05f12481-6692-40a3-9fd6-94d3d849fa0f_default" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DebtInstrumentNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_DebtInstrumentAxis_05f12481-6692-40a3-9fd6-94d3d849fa0f" xlink:to="loc_us-gaap_DebtInstrumentNameDomain_05f12481-6692-40a3-9fd6-94d3d849fa0f_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentNameDomain_9a23e08e-f032-4701-b0d5-5e5d3da7770b" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DebtInstrumentNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_DebtInstrumentAxis_05f12481-6692-40a3-9fd6-94d3d849fa0f" xlink:to="loc_us-gaap_DebtInstrumentNameDomain_9a23e08e-f032-4701-b0d5-5e5d3da7770b" xlink:type="arc" order="1"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.agnc.com/role/DerivativeandOtherHedgingInstrumentsTables" xlink:type="simple" xlink:href="agnc-20220331.xsd#DerivativeandOtherHedgingInstrumentsTables"/>
  <link:definitionLink xlink:role="http://www.agnc.com/role/DerivativeandOtherHedgingInstrumentsTables" xlink:type="extended" id="i5aa1d16aca324270b90aa0556f51c2f6_DerivativeandOtherHedgingInstrumentsTables">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DerivativeLineItems_ec9f9254-804b-456d-bd90-65afc96295df" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DerivativeLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_ScheduleofInterestRateSwapAgreementbyReceiveIndexasapercentageofNotionalAmountTableTextBlock_b6f384d0-a1d9-4644-b03e-0540a3c5d7ca" xlink:href="agnc-20220331.xsd#agnc_ScheduleofInterestRateSwapAgreementbyReceiveIndexasapercentageofNotionalAmountTableTextBlock"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DerivativeLineItems_ec9f9254-804b-456d-bd90-65afc96295df" xlink:to="loc_agnc_ScheduleofInterestRateSwapAgreementbyReceiveIndexasapercentageofNotionalAmountTableTextBlock_b6f384d0-a1d9-4644-b03e-0540a3c5d7ca" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_ScheduleOfOutstandingDerivativesNotDesignatedAsHedgingInstrumentsTableTextBlock_764a9e21-a089-4f8f-aea3-287b90299fd4" xlink:href="agnc-20220331.xsd#agnc_ScheduleOfOutstandingDerivativesNotDesignatedAsHedgingInstrumentsTableTextBlock"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DerivativeLineItems_ec9f9254-804b-456d-bd90-65afc96295df" xlink:to="loc_agnc_ScheduleOfOutstandingDerivativesNotDesignatedAsHedgingInstrumentsTableTextBlock_764a9e21-a089-4f8f-aea3-287b90299fd4" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_ScheduleOfInterestRateSwapAgreementByRemainingMaturityTableTextBlock_1a1ba6f8-1aa2-49dc-9c17-72c4eb9f7b1d" xlink:href="agnc-20220331.xsd#agnc_ScheduleOfInterestRateSwapAgreementByRemainingMaturityTableTextBlock"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DerivativeLineItems_ec9f9254-804b-456d-bd90-65afc96295df" xlink:to="loc_agnc_ScheduleOfInterestRateSwapAgreementByRemainingMaturityTableTextBlock_1a1ba6f8-1aa2-49dc-9c17-72c4eb9f7b1d" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_ScheduleOfInterestRateSwaptionAgreementsOutstandinTableTextBlock_01129a63-3c64-4683-9838-b9606ce9dec7" xlink:href="agnc-20220331.xsd#agnc_ScheduleOfInterestRateSwaptionAgreementsOutstandinTableTextBlock"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DerivativeLineItems_ec9f9254-804b-456d-bd90-65afc96295df" xlink:to="loc_agnc_ScheduleOfInterestRateSwaptionAgreementsOutstandinTableTextBlock_01129a63-3c64-4683-9838-b9606ce9dec7" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_USgovernmentsecuritiesTableTextBlock_40ec216c-8294-4e89-b75b-184d90f36009" xlink:href="agnc-20220331.xsd#agnc_USgovernmentsecuritiesTableTextBlock"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DerivativeLineItems_ec9f9254-804b-456d-bd90-65afc96295df" xlink:to="loc_agnc_USgovernmentsecuritiesTableTextBlock_40ec216c-8294-4e89-b75b-184d90f36009" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_USGovernmentFuturesSecuritiesTableTextBlock_bdaab01e-822c-485e-98ea-0a5765663adf" xlink:href="agnc-20220331.xsd#agnc_USGovernmentFuturesSecuritiesTableTextBlock"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DerivativeLineItems_ec9f9254-804b-456d-bd90-65afc96295df" xlink:to="loc_agnc_USGovernmentFuturesSecuritiesTableTextBlock_bdaab01e-822c-485e-98ea-0a5765663adf" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_ScheduleOfLongAndShortPositionOfDerivativeInstrumentsTableTextBlock_d72b7104-9cd7-4e80-902a-5535c8d5edc4" xlink:href="agnc-20220331.xsd#agnc_ScheduleOfLongAndShortPositionOfDerivativeInstrumentsTableTextBlock"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DerivativeLineItems_ec9f9254-804b-456d-bd90-65afc96295df" xlink:to="loc_agnc_ScheduleOfLongAndShortPositionOfDerivativeInstrumentsTableTextBlock_d72b7104-9cd7-4e80-902a-5535c8d5edc4" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_ScheduleOfOutstandingNotDesignatedAsHedgingInstrumentsTableTextBlock_d9bc7c3e-814a-4098-b348-4ba0a1b4fb4c" xlink:href="agnc-20220331.xsd#agnc_ScheduleOfOutstandingNotDesignatedAsHedgingInstrumentsTableTextBlock"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DerivativeLineItems_ec9f9254-804b-456d-bd90-65afc96295df" xlink:to="loc_agnc_ScheduleOfOutstandingNotDesignatedAsHedgingInstrumentsTableTextBlock_d9bc7c3e-814a-4098-b348-4ba0a1b4fb4c" xlink:type="arc" order="7"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DerivativeTable_45874cb8-e2ad-4d8f-8d3d-62c3a35459db" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DerivativeTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_DerivativeLineItems_ec9f9254-804b-456d-bd90-65afc96295df" xlink:to="loc_us-gaap_DerivativeTable_45874cb8-e2ad-4d8f-8d3d-62c3a35459db" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_HedgingDesignationAxis_02e7a43b-9873-4adc-a884-28aefbfbe44c" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_HedgingDesignationAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_DerivativeTable_45874cb8-e2ad-4d8f-8d3d-62c3a35459db" xlink:to="loc_us-gaap_HedgingDesignationAxis_02e7a43b-9873-4adc-a884-28aefbfbe44c" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_HedgingDesignationDomain_02e7a43b-9873-4adc-a884-28aefbfbe44c_default" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_HedgingDesignationDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_HedgingDesignationAxis_02e7a43b-9873-4adc-a884-28aefbfbe44c" xlink:to="loc_us-gaap_HedgingDesignationDomain_02e7a43b-9873-4adc-a884-28aefbfbe44c_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_HedgingDesignationDomain_45510dfb-9a71-4468-b3fe-c7f681d35ad2" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_HedgingDesignationDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_HedgingDesignationAxis_02e7a43b-9873-4adc-a884-28aefbfbe44c" xlink:to="loc_us-gaap_HedgingDesignationDomain_45510dfb-9a71-4468-b3fe-c7f681d35ad2" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_NondesignatedMember_d7dcc2c9-1dde-48bc-9145-749bcb024447" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_NondesignatedMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_HedgingDesignationDomain_45510dfb-9a71-4468-b3fe-c7f681d35ad2" xlink:to="loc_us-gaap_NondesignatedMember_d7dcc2c9-1dde-48bc-9145-749bcb024447" xlink:type="arc" order="0"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.agnc.com/role/DerivativeandOtherHedgingInstrumentsNarrativeDetails" xlink:type="simple" xlink:href="agnc-20220331.xsd#DerivativeandOtherHedgingInstrumentsNarrativeDetails"/>
  <link:definitionLink xlink:role="http://www.agnc.com/role/DerivativeandOtherHedgingInstrumentsNarrativeDetails" xlink:type="extended" id="if4f645e298624428a84ae58d8ec78ad0_DerivativeandOtherHedgingInstrumentsNarrativeDetails">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StatementLineItems_cc49744a-63db-415b-b233-a027fb3d10cd" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_StatementLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_GainLossOnOtherDebt_a06eb668-3eac-4d22-83f5-a6fc74ffa3c6" xlink:href="agnc-20220331.xsd#agnc_GainLossOnOtherDebt"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_cc49744a-63db-415b-b233-a027fb3d10cd" xlink:to="loc_agnc_GainLossOnOtherDebt_a06eb668-3eac-4d22-83f5-a6fc74ffa3c6" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherComprehensiveIncomeUnrealizedGainLossOnDerivativesArisingDuringPeriodNetOfTax_2d69b59b-583d-4236-8291-5db536242ad0" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_OtherComprehensiveIncomeUnrealizedGainLossOnDerivativesArisingDuringPeriodNetOfTax"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_cc49744a-63db-415b-b233-a027fb3d10cd" xlink:to="loc_us-gaap_OtherComprehensiveIncomeUnrealizedGainLossOnDerivativesArisingDuringPeriodNetOfTax_2d69b59b-583d-4236-8291-5db536242ad0" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DeferredGainLossOnDiscontinuationOfInterestRateFairValueHedge_e3624c0b-bf23-43b7-a85b-6e1741a23f52" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DeferredGainLossOnDiscontinuationOfInterestRateFairValueHedge"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_cc49744a-63db-415b-b233-a027fb3d10cd" xlink:to="loc_us-gaap_DeferredGainLossOnDiscontinuationOfInterestRateFairValueHedge_e3624c0b-bf23-43b7-a85b-6e1741a23f52" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DerivativeAverageRemainingMaturity1_92ba0c59-6e7e-499b-86ea-a60ead1e0da4" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DerivativeAverageRemainingMaturity1"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_cc49744a-63db-415b-b233-a027fb3d10cd" xlink:to="loc_us-gaap_DerivativeAverageRemainingMaturity1_92ba0c59-6e7e-499b-86ea-a60ead1e0da4" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_CashFlowHedgesDerivativeInstrumentsNotDesignatedAsHedgingInstrumentsAverageMonthsToExpiration_739ce70f-a5f0-4d05-9498-2f78d2441602" xlink:href="agnc-20220331.xsd#agnc_CashFlowHedgesDerivativeInstrumentsNotDesignatedAsHedgingInstrumentsAverageMonthsToExpiration"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_cc49744a-63db-415b-b233-a027fb3d10cd" xlink:to="loc_agnc_CashFlowHedgesDerivativeInstrumentsNotDesignatedAsHedgingInstrumentsAverageMonthsToExpiration_739ce70f-a5f0-4d05-9498-2f78d2441602" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DerivativeLiabilityNotionalAmount_670e905c-0326-441a-a317-11007145c901" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DerivativeLiabilityNotionalAmount"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_cc49744a-63db-415b-b233-a027fb3d10cd" xlink:to="loc_us-gaap_DerivativeLiabilityNotionalAmount_670e905c-0326-441a-a317-11007145c901" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DerivativeInstrumentsNotDesignatedAsHedgingInstrumentsGainLossNet_0bb1ca8d-d158-4a20-a7dc-520af17358e0" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DerivativeInstrumentsNotDesignatedAsHedgingInstrumentsGainLossNet"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_cc49744a-63db-415b-b233-a027fb3d10cd" xlink:to="loc_us-gaap_DerivativeInstrumentsNotDesignatedAsHedgingInstrumentsGainLossNet_0bb1ca8d-d158-4a20-a7dc-520af17358e0" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_NotionalAmountOfDerivativesNotDesignatedAsHedgingInstrumentsAdditionsDuringPeriod_dc540824-5942-4467-b35c-7e8145617924" xlink:href="agnc-20220331.xsd#agnc_NotionalAmountOfDerivativesNotDesignatedAsHedgingInstrumentsAdditionsDuringPeriod"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_cc49744a-63db-415b-b233-a027fb3d10cd" xlink:to="loc_agnc_NotionalAmountOfDerivativesNotDesignatedAsHedgingInstrumentsAdditionsDuringPeriod_dc540824-5942-4467-b35c-7e8145617924" xlink:type="arc" order="7"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_NotionalAmountOfDerivativesNotDesignatedAsHedgingInstrumentsSettlementExpirationDuringPeriod_3bf3fe20-2ecb-4dc7-8ff8-904c6a651a2e" xlink:href="agnc-20220331.xsd#agnc_NotionalAmountOfDerivativesNotDesignatedAsHedgingInstrumentsSettlementExpirationDuringPeriod"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_cc49744a-63db-415b-b233-a027fb3d10cd" xlink:to="loc_agnc_NotionalAmountOfDerivativesNotDesignatedAsHedgingInstrumentsSettlementExpirationDuringPeriod_3bf3fe20-2ecb-4dc7-8ff8-904c6a651a2e" xlink:type="arc" order="8"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DerivativeAverageFixedInterestRate_a1463e28-a0c4-44bc-9c17-3b1d5101de15" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DerivativeAverageFixedInterestRate"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_cc49744a-63db-415b-b233-a027fb3d10cd" xlink:to="loc_us-gaap_DerivativeAverageFixedInterestRate_a1463e28-a0c4-44bc-9c17-3b1d5101de15" xlink:type="arc" order="9"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_InterestRateDerivativesAtFairValueNet_9309dc61-46d8-4821-abf8-96b8a59cf8d5" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_InterestRateDerivativesAtFairValueNet"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_cc49744a-63db-415b-b233-a027fb3d10cd" xlink:to="loc_us-gaap_InterestRateDerivativesAtFairValueNet_9309dc61-46d8-4821-abf8-96b8a59cf8d5" xlink:type="arc" order="10"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_OptionsAtCost_bb5a2835-5dcf-46a9-9f38-c04cb17cc284" xlink:href="agnc-20220331.xsd#agnc_OptionsAtCost"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_cc49744a-63db-415b-b233-a027fb3d10cd" xlink:to="loc_agnc_OptionsAtCost_bb5a2835-5dcf-46a9-9f38-c04cb17cc284" xlink:type="arc" order="11"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_InterestRateDerivativeNotDesignatedAsHedgingInstrumentsReceiveRate_adbfcdc9-72e1-4fc6-9d79-0b82d377e75e" xlink:href="agnc-20220331.xsd#agnc_InterestRateDerivativeNotDesignatedAsHedgingInstrumentsReceiveRate"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_cc49744a-63db-415b-b233-a027fb3d10cd" xlink:to="loc_agnc_InterestRateDerivativeNotDesignatedAsHedgingInstrumentsReceiveRate_adbfcdc9-72e1-4fc6-9d79-0b82d377e75e" xlink:type="arc" order="12"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_TradingSecuritiesAddedDuringthePeriod_8da2dd00-1bcf-4dfb-951d-830a3d993f1d" xlink:href="agnc-20220331.xsd#agnc_TradingSecuritiesAddedDuringthePeriod"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_cc49744a-63db-415b-b233-a027fb3d10cd" xlink:to="loc_agnc_TradingSecuritiesAddedDuringthePeriod_8da2dd00-1bcf-4dfb-951d-830a3d993f1d" xlink:type="arc" order="13"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_NotionalAmountOfTradingSecuritiesSettlementExpirationDuringThePeriod_8b4960c8-309f-4b29-848d-fd62a9231121" xlink:href="agnc-20220331.xsd#agnc_NotionalAmountOfTradingSecuritiesSettlementExpirationDuringThePeriod"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_cc49744a-63db-415b-b233-a027fb3d10cd" xlink:to="loc_agnc_NotionalAmountOfTradingSecuritiesSettlementExpirationDuringThePeriod_8b4960c8-309f-4b29-848d-fd62a9231121" xlink:type="arc" order="14"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_TradingSecurities_2cc70a9e-b6f6-4d83-a57a-be14c71707e9" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_TradingSecurities"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_cc49744a-63db-415b-b233-a027fb3d10cd" xlink:to="loc_us-gaap_TradingSecurities_2cc70a9e-b6f6-4d83-a57a-be14c71707e9" xlink:type="arc" order="15"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DerivativeAssets_bb5ac3bd-6de6-4594-be0c-5dd20f71b7e7" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DerivativeAssets"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_cc49744a-63db-415b-b233-a027fb3d10cd" xlink:to="loc_us-gaap_DerivativeAssets_bb5ac3bd-6de6-4594-be0c-5dd20f71b7e7" xlink:type="arc" order="16"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueHedgeLiabilitiesAtFairValue_234e2c8b-5f1f-4952-9dfc-7a6b36f7b89d" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FairValueHedgeLiabilitiesAtFairValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_cc49744a-63db-415b-b233-a027fb3d10cd" xlink:to="loc_us-gaap_FairValueHedgeLiabilitiesAtFairValue_234e2c8b-5f1f-4952-9dfc-7a6b36f7b89d" xlink:type="arc" order="17"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DerivativeFairValueOfDerivativeAsset_d3fdfe1f-96b0-4fdb-8bfd-c1b36c52cbf2" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DerivativeFairValueOfDerivativeAsset"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_cc49744a-63db-415b-b233-a027fb3d10cd" xlink:to="loc_us-gaap_DerivativeFairValueOfDerivativeAsset_d3fdfe1f-96b0-4fdb-8bfd-c1b36c52cbf2" xlink:type="arc" order="18"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DerivativeFairValueOfDerivativeNet_f4e8e878-65fc-4026-9d1a-52372b29629d" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DerivativeFairValueOfDerivativeNet"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_cc49744a-63db-415b-b233-a027fb3d10cd" xlink:to="loc_us-gaap_DerivativeFairValueOfDerivativeNet_f4e8e878-65fc-4026-9d1a-52372b29629d" xlink:type="arc" order="19"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_CreditDefaultSwaps_b950a838-104d-42cc-a3f8-eeb80790545c" xlink:href="agnc-20220331.xsd#agnc_CreditDefaultSwaps"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_cc49744a-63db-415b-b233-a027fb3d10cd" xlink:to="loc_agnc_CreditDefaultSwaps_b950a838-104d-42cc-a3f8-eeb80790545c" xlink:type="arc" order="20"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DerivativeTable_8f971a8f-dc99-4acf-97d4-073bd53a4543" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DerivativeTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_StatementLineItems_cc49744a-63db-415b-b233-a027fb3d10cd" xlink:to="loc_us-gaap_DerivativeTable_8f971a8f-dc99-4acf-97d4-073bd53a4543" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_InvestmentTypeAxis_cc33ae24-cc55-4fcb-a4b1-902074351fb2" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_InvestmentTypeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_DerivativeTable_8f971a8f-dc99-4acf-97d4-073bd53a4543" xlink:to="loc_us-gaap_InvestmentTypeAxis_cc33ae24-cc55-4fcb-a4b1-902074351fb2" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_InvestmentTypeCategorizationMember_cc33ae24-cc55-4fcb-a4b1-902074351fb2_default" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_InvestmentTypeCategorizationMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_InvestmentTypeAxis_cc33ae24-cc55-4fcb-a4b1-902074351fb2" xlink:to="loc_us-gaap_InvestmentTypeCategorizationMember_cc33ae24-cc55-4fcb-a4b1-902074351fb2_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_InvestmentTypeCategorizationMember_94d46cea-a39b-4742-8559-37e9cac88e9c" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_InvestmentTypeCategorizationMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_InvestmentTypeAxis_cc33ae24-cc55-4fcb-a4b1-902074351fb2" xlink:to="loc_us-gaap_InvestmentTypeCategorizationMember_94d46cea-a39b-4742-8559-37e9cac88e9c" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_OtherDerivativesMember_67dadce2-e7c3-4bf8-8aea-af599a8b869a" xlink:href="agnc-20220331.xsd#agnc_OtherDerivativesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_InvestmentTypeCategorizationMember_94d46cea-a39b-4742-8559-37e9cac88e9c" xlink:to="loc_agnc_OtherDerivativesMember_67dadce2-e7c3-4bf8-8aea-af599a8b869a" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PositionAxis_314849ee-d57d-4a62-9333-3887cce92abb" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_PositionAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_DerivativeTable_8f971a8f-dc99-4acf-97d4-073bd53a4543" xlink:to="loc_us-gaap_PositionAxis_314849ee-d57d-4a62-9333-3887cce92abb" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PositionDomain_314849ee-d57d-4a62-9333-3887cce92abb_default" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_PositionDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_PositionAxis_314849ee-d57d-4a62-9333-3887cce92abb" xlink:to="loc_us-gaap_PositionDomain_314849ee-d57d-4a62-9333-3887cce92abb_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PositionDomain_60cee19c-05bb-4447-87b7-a14ba824bf20" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_PositionDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_PositionAxis_314849ee-d57d-4a62-9333-3887cce92abb" xlink:to="loc_us-gaap_PositionDomain_60cee19c-05bb-4447-87b7-a14ba824bf20" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShortMember_2c2bca38-518d-4533-90a4-cd4c89470f6e" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShortMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PositionDomain_60cee19c-05bb-4447-87b7-a14ba824bf20" xlink:to="loc_us-gaap_ShortMember_2c2bca38-518d-4533-90a4-cd4c89470f6e" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LongMember_b92dc2c6-ad75-4ab7-9677-124766a24b00" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_LongMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PositionDomain_60cee19c-05bb-4447-87b7-a14ba824bf20" xlink:to="loc_us-gaap_LongMember_b92dc2c6-ad75-4ab7-9677-124766a24b00" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_HedgingDesignationAxis_92103c51-b2d6-419d-9bde-4399cd963de2" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_HedgingDesignationAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_DerivativeTable_8f971a8f-dc99-4acf-97d4-073bd53a4543" xlink:to="loc_us-gaap_HedgingDesignationAxis_92103c51-b2d6-419d-9bde-4399cd963de2" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_HedgingDesignationDomain_92103c51-b2d6-419d-9bde-4399cd963de2_default" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_HedgingDesignationDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_HedgingDesignationAxis_92103c51-b2d6-419d-9bde-4399cd963de2" xlink:to="loc_us-gaap_HedgingDesignationDomain_92103c51-b2d6-419d-9bde-4399cd963de2_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_HedgingDesignationDomain_a09d5912-eff8-4622-8aa7-423bf4798fb9" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_HedgingDesignationDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_HedgingDesignationAxis_92103c51-b2d6-419d-9bde-4399cd963de2" xlink:to="loc_us-gaap_HedgingDesignationDomain_a09d5912-eff8-4622-8aa7-423bf4798fb9" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_NondesignatedMember_80c5a43d-9125-4011-a54a-f62770bd2f43" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_NondesignatedMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_HedgingDesignationDomain_a09d5912-eff8-4622-8aa7-423bf4798fb9" xlink:to="loc_us-gaap_NondesignatedMember_80c5a43d-9125-4011-a54a-f62770bd2f43" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DerivativeInstrumentRiskAxis_9c97b32d-dad0-4f1d-9f6d-dc439633f39c" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DerivativeInstrumentRiskAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_DerivativeTable_8f971a8f-dc99-4acf-97d4-073bd53a4543" xlink:to="loc_us-gaap_DerivativeInstrumentRiskAxis_9c97b32d-dad0-4f1d-9f6d-dc439633f39c" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DerivativeContractTypeDomain_9c97b32d-dad0-4f1d-9f6d-dc439633f39c_default" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DerivativeContractTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_DerivativeInstrumentRiskAxis_9c97b32d-dad0-4f1d-9f6d-dc439633f39c" xlink:to="loc_us-gaap_DerivativeContractTypeDomain_9c97b32d-dad0-4f1d-9f6d-dc439633f39c_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DerivativeContractTypeDomain_91083ac5-e9fe-4206-97c4-9a01d57df409" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DerivativeContractTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_DerivativeInstrumentRiskAxis_9c97b32d-dad0-4f1d-9f6d-dc439633f39c" xlink:to="loc_us-gaap_DerivativeContractTypeDomain_91083ac5-e9fe-4206-97c4-9a01d57df409" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FutureMember_513ef977-521d-479d-b743-86f618941e07" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FutureMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DerivativeContractTypeDomain_91083ac5-e9fe-4206-97c4-9a01d57df409" xlink:to="loc_us-gaap_FutureMember_513ef977-521d-479d-b743-86f618941e07" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ForwardContractsMember_f5000c2a-1ef8-4d39-b0c2-a45b53ec2f9b" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ForwardContractsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DerivativeContractTypeDomain_91083ac5-e9fe-4206-97c4-9a01d57df409" xlink:to="loc_us-gaap_ForwardContractsMember_f5000c2a-1ef8-4d39-b0c2-a45b53ec2f9b" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_InterestRateSwaptionMember_9a1ee47e-1157-414c-bfa5-b637121b935f" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_InterestRateSwaptionMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DerivativeContractTypeDomain_91083ac5-e9fe-4206-97c4-9a01d57df409" xlink:to="loc_us-gaap_InterestRateSwaptionMember_9a1ee47e-1157-414c-bfa5-b637121b935f" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_TBAAndForwardSettlingSecuritiesMember_877e6ec5-398d-43f1-92fb-ed0ef3e63648" xlink:href="agnc-20220331.xsd#agnc_TBAAndForwardSettlingSecuritiesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DerivativeContractTypeDomain_91083ac5-e9fe-4206-97c4-9a01d57df409" xlink:to="loc_agnc_TBAAndForwardSettlingSecuritiesMember_877e6ec5-398d-43f1-92fb-ed0ef3e63648" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_USTreasurySecuritiesMember_186baf6f-3024-4cbf-bc11-d9ff49770b18" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_USTreasurySecuritiesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DerivativeContractTypeDomain_91083ac5-e9fe-4206-97c4-9a01d57df409" xlink:to="loc_us-gaap_USTreasurySecuritiesMember_186baf6f-3024-4cbf-bc11-d9ff49770b18" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CreditDefaultSwapMember_12d1e786-fe7d-4efa-b88c-b2190bfa23ed" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_CreditDefaultSwapMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DerivativeContractTypeDomain_91083ac5-e9fe-4206-97c4-9a01d57df409" xlink:to="loc_us-gaap_CreditDefaultSwapMember_12d1e786-fe7d-4efa-b88c-b2190bfa23ed" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DerivativeContractTypeDomain_a92a8d2b-6323-4b2b-aee5-1ae59213c834" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DerivativeContractTypeDomain"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_DerivativePositionAxis_ce014691-7e32-49bd-bb9a-6f71155b3487" xlink:href="agnc-20220331.xsd#agnc_DerivativePositionAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_DerivativeTable_8f971a8f-dc99-4acf-97d4-073bd53a4543" xlink:to="loc_agnc_DerivativePositionAxis_ce014691-7e32-49bd-bb9a-6f71155b3487" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_DerivativePositionDomain_ce014691-7e32-49bd-bb9a-6f71155b3487_default" xlink:href="agnc-20220331.xsd#agnc_DerivativePositionDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_agnc_DerivativePositionAxis_ce014691-7e32-49bd-bb9a-6f71155b3487" xlink:to="loc_agnc_DerivativePositionDomain_ce014691-7e32-49bd-bb9a-6f71155b3487_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_DerivativePositionDomain_48ce5d28-c360-4ede-9fb5-a754fa7feec4" xlink:href="agnc-20220331.xsd#agnc_DerivativePositionDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_agnc_DerivativePositionAxis_ce014691-7e32-49bd-bb9a-6f71155b3487" xlink:to="loc_agnc_DerivativePositionDomain_48ce5d28-c360-4ede-9fb5-a754fa7feec4" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_InterestRateSwapMember_1a873701-5e86-4888-8a63-caaaba0fec7e" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_InterestRateSwapMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_agnc_DerivativePositionDomain_48ce5d28-c360-4ede-9fb5-a754fa7feec4" xlink:to="loc_us-gaap_InterestRateSwapMember_1a873701-5e86-4888-8a63-caaaba0fec7e" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncomeStatementLocationAxis_431a1c94-9eb4-4c13-aa61-3058f37569eb" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_IncomeStatementLocationAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_DerivativeTable_8f971a8f-dc99-4acf-97d4-073bd53a4543" xlink:to="loc_us-gaap_IncomeStatementLocationAxis_431a1c94-9eb4-4c13-aa61-3058f37569eb" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncomeStatementLocationDomain_431a1c94-9eb4-4c13-aa61-3058f37569eb_default" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_IncomeStatementLocationDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_IncomeStatementLocationAxis_431a1c94-9eb4-4c13-aa61-3058f37569eb" xlink:to="loc_us-gaap_IncomeStatementLocationDomain_431a1c94-9eb4-4c13-aa61-3058f37569eb_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncomeStatementLocationDomain_b25fea6d-0e37-4ae8-bafb-169cda997622" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_IncomeStatementLocationDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_IncomeStatementLocationAxis_431a1c94-9eb4-4c13-aa61-3058f37569eb" xlink:to="loc_us-gaap_IncomeStatementLocationDomain_b25fea6d-0e37-4ae8-bafb-169cda997622" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_InterestOnlyAndPrincipalOnlyStripMember_73d7b37c-91a9-48ed-8015-842fc5c40e48" xlink:href="agnc-20220331.xsd#agnc_InterestOnlyAndPrincipalOnlyStripMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncomeStatementLocationDomain_b25fea6d-0e37-4ae8-bafb-169cda997622" xlink:to="loc_agnc_InterestOnlyAndPrincipalOnlyStripMember_73d7b37c-91a9-48ed-8015-842fc5c40e48" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AdjustmentsForChangeInAccountingPrincipleAxis_55257bc1-4fb5-40a3-b34a-dd534a31dd77" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AdjustmentsForChangeInAccountingPrincipleAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_DerivativeTable_8f971a8f-dc99-4acf-97d4-073bd53a4543" xlink:to="loc_us-gaap_AdjustmentsForChangeInAccountingPrincipleAxis_55257bc1-4fb5-40a3-b34a-dd534a31dd77" xlink:type="arc" order="7"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ChangeInAccountingPrincipleMember_55257bc1-4fb5-40a3-b34a-dd534a31dd77_default" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ChangeInAccountingPrincipleMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_AdjustmentsForChangeInAccountingPrincipleAxis_55257bc1-4fb5-40a3-b34a-dd534a31dd77" xlink:to="loc_us-gaap_ChangeInAccountingPrincipleMember_55257bc1-4fb5-40a3-b34a-dd534a31dd77_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ChangeInAccountingPrincipleMember_b4a32e49-c5f3-4577-98f5-05e87aef94e5" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ChangeInAccountingPrincipleMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_AdjustmentsForChangeInAccountingPrincipleAxis_55257bc1-4fb5-40a3-b34a-dd534a31dd77" xlink:to="loc_us-gaap_ChangeInAccountingPrincipleMember_b4a32e49-c5f3-4577-98f5-05e87aef94e5" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_DiscontinuationOfElectionToAccountForInterestRateSwapsAsDesignatedCashFlowHedgesMember_50977e0c-ad2e-42d8-b2f7-1dcc370ac00b" xlink:href="agnc-20220331.xsd#agnc_DiscontinuationOfElectionToAccountForInterestRateSwapsAsDesignatedCashFlowHedgesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ChangeInAccountingPrincipleMember_b4a32e49-c5f3-4577-98f5-05e87aef94e5" xlink:to="loc_agnc_DiscontinuationOfElectionToAccountForInterestRateSwapsAsDesignatedCashFlowHedgesMember_50977e0c-ad2e-42d8-b2f7-1dcc370ac00b" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DerivativeInstrumentRiskAxis_02a63fba-c3c1-4163-a348-0e84ef7f1ab3" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DerivativeInstrumentRiskAxis"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DerivativeContractTypeDomain_02a63fba-c3c1-4163-a348-0e84ef7f1ab3_default" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DerivativeContractTypeDomain"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_DerivativeInstrumentsDesignationAxis_ea5142e4-f661-4431-ab53-6f61e3d45514" xlink:href="agnc-20220331.xsd#agnc_DerivativeInstrumentsDesignationAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_DerivativeTable_8f971a8f-dc99-4acf-97d4-073bd53a4543" xlink:to="loc_agnc_DerivativeInstrumentsDesignationAxis_ea5142e4-f661-4431-ab53-6f61e3d45514" xlink:type="arc" order="9"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_DerivativeInstrumentsDesignationDomain_ea5142e4-f661-4431-ab53-6f61e3d45514_default" xlink:href="agnc-20220331.xsd#agnc_DerivativeInstrumentsDesignationDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_agnc_DerivativeInstrumentsDesignationAxis_ea5142e4-f661-4431-ab53-6f61e3d45514" xlink:to="loc_agnc_DerivativeInstrumentsDesignationDomain_ea5142e4-f661-4431-ab53-6f61e3d45514_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_DerivativeInstrumentsDesignationDomain_fe06252e-30c4-40f4-96b3-4bc56e1ddb3a" xlink:href="agnc-20220331.xsd#agnc_DerivativeInstrumentsDesignationDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_agnc_DerivativeInstrumentsDesignationAxis_ea5142e4-f661-4431-ab53-6f61e3d45514" xlink:to="loc_agnc_DerivativeInstrumentsDesignationDomain_fe06252e-30c4-40f4-96b3-4bc56e1ddb3a" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_AtCostBasisMember_74a90546-6724-4628-a8f7-77a5aa44537b" xlink:href="agnc-20220331.xsd#agnc_AtCostBasisMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_agnc_DerivativeInstrumentsDesignationDomain_fe06252e-30c4-40f4-96b3-4bc56e1ddb3a" xlink:to="loc_agnc_AtCostBasisMember_74a90546-6724-4628-a8f7-77a5aa44537b" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_AtCarryingValueMember_c24cf84b-f6b4-4f2a-814c-b317c2dadcc1" xlink:href="agnc-20220331.xsd#agnc_AtCarryingValueMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_agnc_DerivativeInstrumentsDesignationDomain_fe06252e-30c4-40f4-96b3-4bc56e1ddb3a" xlink:to="loc_agnc_AtCarryingValueMember_c24cf84b-f6b4-4f2a-814c-b317c2dadcc1" xlink:type="arc" order="1"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.agnc.com/role/DerivativeandOtherHedgingInstrumentsFairValueInformationDetails" xlink:type="simple" xlink:href="agnc-20220331.xsd#DerivativeandOtherHedgingInstrumentsFairValueInformationDetails"/>
  <link:definitionLink xlink:role="http://www.agnc.com/role/DerivativeandOtherHedgingInstrumentsFairValueInformationDetails" xlink:type="extended" id="i35e332aca6a649999983a1b717a599a8_DerivativeandOtherHedgingInstrumentsFairValueInformationDetails">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DerivativeLineItems_c230027c-8460-4a33-9ea1-1c5debc8975a" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DerivativeLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DerivativeLiabilityNotionalAmount_4614f200-20e9-4930-9b58-f4231f29403e" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DerivativeLiabilityNotionalAmount"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DerivativeLineItems_c230027c-8460-4a33-9ea1-1c5debc8975a" xlink:to="loc_us-gaap_DerivativeLiabilityNotionalAmount_4614f200-20e9-4930-9b58-f4231f29403e" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DerivativeInstrumentsNotDesignatedAsHedgingInstrumentsAssetAtFairValue_bb8178d5-411f-402c-ba76-ac4ac12ac6b0" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DerivativeInstrumentsNotDesignatedAsHedgingInstrumentsAssetAtFairValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DerivativeLineItems_c230027c-8460-4a33-9ea1-1c5debc8975a" xlink:to="loc_us-gaap_DerivativeInstrumentsNotDesignatedAsHedgingInstrumentsAssetAtFairValue_bb8178d5-411f-402c-ba76-ac4ac12ac6b0" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DerivativeInstrumentsNotDesignatedAsHedgingInstrumentsLiabilityAtFairValue_cb813aed-28e2-4c35-87de-f81c75606d62" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DerivativeInstrumentsNotDesignatedAsHedgingInstrumentsLiabilityAtFairValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DerivativeLineItems_c230027c-8460-4a33-9ea1-1c5debc8975a" xlink:to="loc_us-gaap_DerivativeInstrumentsNotDesignatedAsHedgingInstrumentsLiabilityAtFairValue_cb813aed-28e2-4c35-87de-f81c75606d62" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DerivativeAssets_c7ac54d7-30b5-4255-a5bc-be05e406108b" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DerivativeAssets"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DerivativeLineItems_c230027c-8460-4a33-9ea1-1c5debc8975a" xlink:to="loc_us-gaap_DerivativeAssets_c7ac54d7-30b5-4255-a5bc-be05e406108b" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DerivativeLiabilities_cd2f7426-9a8e-46f3-b51b-6b3ce6e00fd1" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DerivativeLiabilities"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DerivativeLineItems_c230027c-8460-4a33-9ea1-1c5debc8975a" xlink:to="loc_us-gaap_DerivativeLiabilities_cd2f7426-9a8e-46f3-b51b-6b3ce6e00fd1" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FinancialInstrumentsOwnedUSGovernmentAndAgencyObligationsAtFairValue_e3c12ad1-735f-43e8-8105-be32a978c7c2" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FinancialInstrumentsOwnedUSGovernmentAndAgencyObligationsAtFairValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DerivativeLineItems_c230027c-8460-4a33-9ea1-1c5debc8975a" xlink:to="loc_us-gaap_FinancialInstrumentsOwnedUSGovernmentAndAgencyObligationsAtFairValue_e3c12ad1-735f-43e8-8105-be32a978c7c2" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FinancialInstrumentsSoldNotYetPurchasedUSGovernmentAndAgencyObligations_9f7056a6-90c6-411b-8c53-8e6f13bf1d77" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FinancialInstrumentsSoldNotYetPurchasedUSGovernmentAndAgencyObligations"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DerivativeLineItems_c230027c-8460-4a33-9ea1-1c5debc8975a" xlink:to="loc_us-gaap_FinancialInstrumentsSoldNotYetPurchasedUSGovernmentAndAgencyObligations_9f7056a6-90c6-411b-8c53-8e6f13bf1d77" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_Governmentbondsownedandsoldshortnet_141ee122-21bb-4fa3-91d8-e6554ba38d1e" xlink:href="agnc-20220331.xsd#agnc_Governmentbondsownedandsoldshortnet"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DerivativeLineItems_c230027c-8460-4a33-9ea1-1c5debc8975a" xlink:to="loc_agnc_Governmentbondsownedandsoldshortnet_141ee122-21bb-4fa3-91d8-e6554ba38d1e" xlink:type="arc" order="7"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_NotionalAmountOfDerivativesNotDesignatedAsHedgingInstrumentsAdditionsDuringPeriod_8eed8a78-8a2f-4f59-be60-5a743e755306" xlink:href="agnc-20220331.xsd#agnc_NotionalAmountOfDerivativesNotDesignatedAsHedgingInstrumentsAdditionsDuringPeriod"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DerivativeLineItems_c230027c-8460-4a33-9ea1-1c5debc8975a" xlink:to="loc_agnc_NotionalAmountOfDerivativesNotDesignatedAsHedgingInstrumentsAdditionsDuringPeriod_8eed8a78-8a2f-4f59-be60-5a743e755306" xlink:type="arc" order="8"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_NotionalAmountOfDerivativesNotDesignatedAsHedgingInstrumentsSettlementExpirationDuringPeriod_33eebe51-a5f9-4832-930e-f78dd0752a63" xlink:href="agnc-20220331.xsd#agnc_NotionalAmountOfDerivativesNotDesignatedAsHedgingInstrumentsSettlementExpirationDuringPeriod"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DerivativeLineItems_c230027c-8460-4a33-9ea1-1c5debc8975a" xlink:to="loc_agnc_NotionalAmountOfDerivativesNotDesignatedAsHedgingInstrumentsSettlementExpirationDuringPeriod_33eebe51-a5f9-4832-930e-f78dd0752a63" xlink:type="arc" order="9"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DerivativeInstrumentsNotDesignatedAsHedgingInstrumentsGainLossNet_c8f40907-8c45-4320-b4c5-0a629b9901a0" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DerivativeInstrumentsNotDesignatedAsHedgingInstrumentsGainLossNet"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DerivativeLineItems_c230027c-8460-4a33-9ea1-1c5debc8975a" xlink:to="loc_us-gaap_DerivativeInstrumentsNotDesignatedAsHedgingInstrumentsGainLossNet_c8f40907-8c45-4320-b4c5-0a629b9901a0" xlink:type="arc" order="10"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_TradingSecurities_4e7a3884-1cbf-416b-ac44-ced3747f2861" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_TradingSecurities"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DerivativeLineItems_c230027c-8460-4a33-9ea1-1c5debc8975a" xlink:to="loc_us-gaap_TradingSecurities_4e7a3884-1cbf-416b-ac44-ced3747f2861" xlink:type="arc" order="11"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_TradingSecuritiesAddedDuringthePeriod_699b8673-a48b-4f45-8895-dd00d26c341b" xlink:href="agnc-20220331.xsd#agnc_TradingSecuritiesAddedDuringthePeriod"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DerivativeLineItems_c230027c-8460-4a33-9ea1-1c5debc8975a" xlink:to="loc_agnc_TradingSecuritiesAddedDuringthePeriod_699b8673-a48b-4f45-8895-dd00d26c341b" xlink:type="arc" order="12"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_NotionalAmountOfTradingSecuritiesSettlementExpirationDuringThePeriod_27e94261-97a7-4a4f-b6fd-a67bd564de95" xlink:href="agnc-20220331.xsd#agnc_NotionalAmountOfTradingSecuritiesSettlementExpirationDuringThePeriod"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DerivativeLineItems_c230027c-8460-4a33-9ea1-1c5debc8975a" xlink:to="loc_agnc_NotionalAmountOfTradingSecuritiesSettlementExpirationDuringThePeriod_27e94261-97a7-4a4f-b6fd-a67bd564de95" xlink:type="arc" order="13"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_OtherDerivativeAsset_e0b75e35-30ed-4ba5-81a4-09a1e09b5b12" xlink:href="agnc-20220331.xsd#agnc_OtherDerivativeAsset"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DerivativeLineItems_c230027c-8460-4a33-9ea1-1c5debc8975a" xlink:to="loc_agnc_OtherDerivativeAsset_e0b75e35-30ed-4ba5-81a4-09a1e09b5b12" xlink:type="arc" order="14"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_NetFairValueOfInterestRateSwapsExcludingTheRecognitionOfVariationMarginSettlementsAsAReductionOfCarryingValue_d57b93c3-44ec-40b4-950f-77956329fecc" xlink:href="agnc-20220331.xsd#agnc_NetFairValueOfInterestRateSwapsExcludingTheRecognitionOfVariationMarginSettlementsAsAReductionOfCarryingValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DerivativeLineItems_c230027c-8460-4a33-9ea1-1c5debc8975a" xlink:to="loc_agnc_NetFairValueOfInterestRateSwapsExcludingTheRecognitionOfVariationMarginSettlementsAsAReductionOfCarryingValue_d57b93c3-44ec-40b4-950f-77956329fecc" xlink:type="arc" order="15"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DerivativeTable_06b56389-b1b5-45b6-8c35-10e3be00d62f" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DerivativeTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_DerivativeLineItems_c230027c-8460-4a33-9ea1-1c5debc8975a" xlink:to="loc_us-gaap_DerivativeTable_06b56389-b1b5-45b6-8c35-10e3be00d62f" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PositionAxis_9af0b517-d089-4f60-80ac-5dce522fb7f6" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_PositionAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_DerivativeTable_06b56389-b1b5-45b6-8c35-10e3be00d62f" xlink:to="loc_us-gaap_PositionAxis_9af0b517-d089-4f60-80ac-5dce522fb7f6" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PositionDomain_9af0b517-d089-4f60-80ac-5dce522fb7f6_default" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_PositionDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_PositionAxis_9af0b517-d089-4f60-80ac-5dce522fb7f6" xlink:to="loc_us-gaap_PositionDomain_9af0b517-d089-4f60-80ac-5dce522fb7f6_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PositionDomain_dad0563d-5713-44f5-860f-a36337ae3b81" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_PositionDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_PositionAxis_9af0b517-d089-4f60-80ac-5dce522fb7f6" xlink:to="loc_us-gaap_PositionDomain_dad0563d-5713-44f5-860f-a36337ae3b81" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShortMember_4955c6d6-3687-4a0f-894f-4df2e0a34b45" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShortMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PositionDomain_dad0563d-5713-44f5-860f-a36337ae3b81" xlink:to="loc_us-gaap_ShortMember_4955c6d6-3687-4a0f-894f-4df2e0a34b45" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LongMember_1fec113c-1e48-4e9a-9a0d-115bf2d03692" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_LongMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PositionDomain_dad0563d-5713-44f5-860f-a36337ae3b81" xlink:to="loc_us-gaap_LongMember_1fec113c-1e48-4e9a-9a0d-115bf2d03692" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_HedgingDesignationAxis_2cc06f85-ca8b-43a1-a217-5091ee58de55" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_HedgingDesignationAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_DerivativeTable_06b56389-b1b5-45b6-8c35-10e3be00d62f" xlink:to="loc_us-gaap_HedgingDesignationAxis_2cc06f85-ca8b-43a1-a217-5091ee58de55" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_HedgingDesignationDomain_2cc06f85-ca8b-43a1-a217-5091ee58de55_default" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_HedgingDesignationDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_HedgingDesignationAxis_2cc06f85-ca8b-43a1-a217-5091ee58de55" xlink:to="loc_us-gaap_HedgingDesignationDomain_2cc06f85-ca8b-43a1-a217-5091ee58de55_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_HedgingDesignationDomain_4c031181-e24c-4619-9fab-30fa4ff9962d" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_HedgingDesignationDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_HedgingDesignationAxis_2cc06f85-ca8b-43a1-a217-5091ee58de55" xlink:to="loc_us-gaap_HedgingDesignationDomain_4c031181-e24c-4619-9fab-30fa4ff9962d" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_NondesignatedMember_67adb77a-224d-4fd6-a295-131c1f1b6256" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_NondesignatedMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_HedgingDesignationDomain_4c031181-e24c-4619-9fab-30fa4ff9962d" xlink:to="loc_us-gaap_NondesignatedMember_67adb77a-224d-4fd6-a295-131c1f1b6256" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueByAssetClassAxis_cf994543-ef2f-405d-989d-49239bf18602" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FairValueByAssetClassAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_DerivativeTable_06b56389-b1b5-45b6-8c35-10e3be00d62f" xlink:to="loc_us-gaap_FairValueByAssetClassAxis_cf994543-ef2f-405d-989d-49239bf18602" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueAssetsMeasuredOnRecurringBasisUnobservableInputReconciliationByAssetClassDomain_cf994543-ef2f-405d-989d-49239bf18602_default" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FairValueAssetsMeasuredOnRecurringBasisUnobservableInputReconciliationByAssetClassDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_FairValueByAssetClassAxis_cf994543-ef2f-405d-989d-49239bf18602" xlink:to="loc_us-gaap_FairValueAssetsMeasuredOnRecurringBasisUnobservableInputReconciliationByAssetClassDomain_cf994543-ef2f-405d-989d-49239bf18602_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueAssetsMeasuredOnRecurringBasisUnobservableInputReconciliationByAssetClassDomain_f53ee947-dc86-4f8c-870f-4857f657f57b" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FairValueAssetsMeasuredOnRecurringBasisUnobservableInputReconciliationByAssetClassDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_FairValueByAssetClassAxis_cf994543-ef2f-405d-989d-49239bf18602" xlink:to="loc_us-gaap_FairValueAssetsMeasuredOnRecurringBasisUnobservableInputReconciliationByAssetClassDomain_f53ee947-dc86-4f8c-870f-4857f657f57b" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_USTreasurySecuritiesMember_8051fd72-9553-43f7-855e-148bd478c2ad" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_USTreasurySecuritiesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FairValueAssetsMeasuredOnRecurringBasisUnobservableInputReconciliationByAssetClassDomain_f53ee947-dc86-4f8c-870f-4857f657f57b" xlink:to="loc_us-gaap_USTreasurySecuritiesMember_8051fd72-9553-43f7-855e-148bd478c2ad" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_TBAAndForwardSettlingSecuritiesMember_3610d13a-640c-4fd6-86c8-6bf366e5471f" xlink:href="agnc-20220331.xsd#agnc_TBAAndForwardSettlingSecuritiesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FairValueAssetsMeasuredOnRecurringBasisUnobservableInputReconciliationByAssetClassDomain_f53ee947-dc86-4f8c-870f-4857f657f57b" xlink:to="loc_agnc_TBAAndForwardSettlingSecuritiesMember_3610d13a-640c-4fd6-86c8-6bf366e5471f" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_SaleOfTBAAndForwardSettlingSecuritiesMember_ccf83524-7501-4cd3-bac7-c5f44b9187b8" xlink:href="agnc-20220331.xsd#agnc_SaleOfTBAAndForwardSettlingSecuritiesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FairValueAssetsMeasuredOnRecurringBasisUnobservableInputReconciliationByAssetClassDomain_f53ee947-dc86-4f8c-870f-4857f657f57b" xlink:to="loc_agnc_SaleOfTBAAndForwardSettlingSecuritiesMember_ccf83524-7501-4cd3-bac7-c5f44b9187b8" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueByMeasurementFrequencyAxis_abd841f9-f298-44f0-98dd-e9e8784a5b53" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FairValueByMeasurementFrequencyAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_DerivativeTable_06b56389-b1b5-45b6-8c35-10e3be00d62f" xlink:to="loc_us-gaap_FairValueByMeasurementFrequencyAxis_abd841f9-f298-44f0-98dd-e9e8784a5b53" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueMeasurementFrequencyDomain_abd841f9-f298-44f0-98dd-e9e8784a5b53_default" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FairValueMeasurementFrequencyDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_FairValueByMeasurementFrequencyAxis_abd841f9-f298-44f0-98dd-e9e8784a5b53" xlink:to="loc_us-gaap_FairValueMeasurementFrequencyDomain_abd841f9-f298-44f0-98dd-e9e8784a5b53_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueMeasurementFrequencyDomain_18f6a58c-aa85-4364-9b10-9d0a3187c4c3" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FairValueMeasurementFrequencyDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_FairValueByMeasurementFrequencyAxis_abd841f9-f298-44f0-98dd-e9e8784a5b53" xlink:to="loc_us-gaap_FairValueMeasurementFrequencyDomain_18f6a58c-aa85-4364-9b10-9d0a3187c4c3" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueMeasurementsRecurringMember_2d9a202e-4342-43c9-8662-8d312ed1d4c7" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FairValueMeasurementsRecurringMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FairValueMeasurementFrequencyDomain_18f6a58c-aa85-4364-9b10-9d0a3187c4c3" xlink:to="loc_us-gaap_FairValueMeasurementsRecurringMember_2d9a202e-4342-43c9-8662-8d312ed1d4c7" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DerivativeInstrumentRiskAxis_c10f65cc-0333-4540-924e-10ed2ce5df4d" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DerivativeInstrumentRiskAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_DerivativeTable_06b56389-b1b5-45b6-8c35-10e3be00d62f" xlink:to="loc_us-gaap_DerivativeInstrumentRiskAxis_c10f65cc-0333-4540-924e-10ed2ce5df4d" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DerivativeContractTypeDomain_c10f65cc-0333-4540-924e-10ed2ce5df4d_default" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DerivativeContractTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_DerivativeInstrumentRiskAxis_c10f65cc-0333-4540-924e-10ed2ce5df4d" xlink:to="loc_us-gaap_DerivativeContractTypeDomain_c10f65cc-0333-4540-924e-10ed2ce5df4d_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DerivativeContractTypeDomain_0677077b-f41d-488f-b596-23d568bd7a9a" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DerivativeContractTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_DerivativeInstrumentRiskAxis_c10f65cc-0333-4540-924e-10ed2ce5df4d" xlink:to="loc_us-gaap_DerivativeContractTypeDomain_0677077b-f41d-488f-b596-23d568bd7a9a" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_TBAAndForwardSettlingSecuritiesMember_324895f9-7b4d-4e20-9f35-9c5a754af08e" xlink:href="agnc-20220331.xsd#agnc_TBAAndForwardSettlingSecuritiesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DerivativeContractTypeDomain_0677077b-f41d-488f-b596-23d568bd7a9a" xlink:to="loc_agnc_TBAAndForwardSettlingSecuritiesMember_324895f9-7b4d-4e20-9f35-9c5a754af08e" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_InterestRateSwapMember_a9242248-2b6f-4656-9bd0-2bffa49edfa0" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_InterestRateSwapMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DerivativeContractTypeDomain_0677077b-f41d-488f-b596-23d568bd7a9a" xlink:to="loc_us-gaap_InterestRateSwapMember_a9242248-2b6f-4656-9bd0-2bffa49edfa0" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_InterestRateSwaptionMember_ae85fdf5-aadf-49d0-8508-d6d2a12ab2be" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_InterestRateSwaptionMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DerivativeContractTypeDomain_0677077b-f41d-488f-b596-23d568bd7a9a" xlink:to="loc_us-gaap_InterestRateSwaptionMember_ae85fdf5-aadf-49d0-8508-d6d2a12ab2be" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_PurchasesOfTBAsAndForwardSettlingSecuritiesMember_5eb7f8b0-a659-4308-ae5f-ca0f4626fb16" xlink:href="agnc-20220331.xsd#agnc_PurchasesOfTBAsAndForwardSettlingSecuritiesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DerivativeContractTypeDomain_0677077b-f41d-488f-b596-23d568bd7a9a" xlink:to="loc_agnc_PurchasesOfTBAsAndForwardSettlingSecuritiesMember_5eb7f8b0-a659-4308-ae5f-ca0f4626fb16" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FutureMember_e0534db6-8db3-4099-90de-4dce852d10e7" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FutureMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DerivativeContractTypeDomain_0677077b-f41d-488f-b596-23d568bd7a9a" xlink:to="loc_us-gaap_FutureMember_e0534db6-8db3-4099-90de-4dce852d10e7" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_USTreasurySecuritiesMember_109f5853-99db-46ee-a194-d3f9309de7fb" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_USTreasurySecuritiesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DerivativeContractTypeDomain_0677077b-f41d-488f-b596-23d568bd7a9a" xlink:to="loc_us-gaap_USTreasurySecuritiesMember_109f5853-99db-46ee-a194-d3f9309de7fb" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CreditDefaultSwapMember_ff0b68a4-ed86-499c-8ae6-e5a4b6a5ca25" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_CreditDefaultSwapMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DerivativeContractTypeDomain_0677077b-f41d-488f-b596-23d568bd7a9a" xlink:to="loc_us-gaap_CreditDefaultSwapMember_ff0b68a4-ed86-499c-8ae6-e5a4b6a5ca25" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueByFairValueHierarchyLevelAxis_cca9fdfa-ebb9-427d-9026-b1c26ca1d296" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FairValueByFairValueHierarchyLevelAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_DerivativeTable_06b56389-b1b5-45b6-8c35-10e3be00d62f" xlink:to="loc_us-gaap_FairValueByFairValueHierarchyLevelAxis_cca9fdfa-ebb9-427d-9026-b1c26ca1d296" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueMeasurementsFairValueHierarchyDomain_cca9fdfa-ebb9-427d-9026-b1c26ca1d296_default" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FairValueMeasurementsFairValueHierarchyDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_FairValueByFairValueHierarchyLevelAxis_cca9fdfa-ebb9-427d-9026-b1c26ca1d296" xlink:to="loc_us-gaap_FairValueMeasurementsFairValueHierarchyDomain_cca9fdfa-ebb9-427d-9026-b1c26ca1d296_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueMeasurementsFairValueHierarchyDomain_5519e2ad-4f9a-42c6-8e23-0dd64eb6a6aa" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FairValueMeasurementsFairValueHierarchyDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_FairValueByFairValueHierarchyLevelAxis_cca9fdfa-ebb9-427d-9026-b1c26ca1d296" xlink:to="loc_us-gaap_FairValueMeasurementsFairValueHierarchyDomain_5519e2ad-4f9a-42c6-8e23-0dd64eb6a6aa" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueInputsLevel2Member_716de651-782f-443d-9236-893a6d81f6cd" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FairValueInputsLevel2Member"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FairValueMeasurementsFairValueHierarchyDomain_5519e2ad-4f9a-42c6-8e23-0dd64eb6a6aa" xlink:to="loc_us-gaap_FairValueInputsLevel2Member_716de651-782f-443d-9236-893a6d81f6cd" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueInputsLevel1Member_141832de-1a27-4229-98a5-6582b6d4a2d2" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FairValueInputsLevel1Member"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FairValueMeasurementsFairValueHierarchyDomain_5519e2ad-4f9a-42c6-8e23-0dd64eb6a6aa" xlink:to="loc_us-gaap_FairValueInputsLevel1Member_141832de-1a27-4229-98a5-6582b6d4a2d2" xlink:type="arc" order="1"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.agnc.com/role/DerivativeandOtherHedgingInstrumentsSummaryOfOutstandingInterestRateSwapsDetails" xlink:type="simple" xlink:href="agnc-20220331.xsd#DerivativeandOtherHedgingInstrumentsSummaryOfOutstandingInterestRateSwapsDetails"/>
  <link:definitionLink xlink:role="http://www.agnc.com/role/DerivativeandOtherHedgingInstrumentsSummaryOfOutstandingInterestRateSwapsDetails" xlink:type="extended" id="id91e80acf53f43cfa98fa7b12edc0e1e_DerivativeandOtherHedgingInstrumentsSummaryOfOutstandingInterestRateSwapsDetails">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StatementLineItems_9dd171e3-0716-4992-8ece-0cd48a924e9d" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_StatementLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_InterestRateSwapsLinkedtoOvernightIndexSwapRate_97dab66c-927d-4db8-b276-f8476a659e80" xlink:href="agnc-20220331.xsd#agnc_InterestRateSwapsLinkedtoOvernightIndexSwapRate"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_9dd171e3-0716-4992-8ece-0cd48a924e9d" xlink:to="loc_agnc_InterestRateSwapsLinkedtoOvernightIndexSwapRate_97dab66c-927d-4db8-b276-f8476a659e80" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_GainLossOnOtherDebt_208acfe9-b0f4-49ec-a660-b45d52f8fcc8" xlink:href="agnc-20220331.xsd#agnc_GainLossOnOtherDebt"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_9dd171e3-0716-4992-8ece-0cd48a924e9d" xlink:to="loc_agnc_GainLossOnOtherDebt_208acfe9-b0f4-49ec-a660-b45d52f8fcc8" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DerivativeInstrumentsNotDesignatedAsHedgingInstrumentsGainLossNet_cd96cbb2-46e3-4ed8-81ca-19b229021b06" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DerivativeInstrumentsNotDesignatedAsHedgingInstrumentsGainLossNet"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_9dd171e3-0716-4992-8ece-0cd48a924e9d" xlink:to="loc_us-gaap_DerivativeInstrumentsNotDesignatedAsHedgingInstrumentsGainLossNet_cd96cbb2-46e3-4ed8-81ca-19b229021b06" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DerivativeLiabilityNotionalAmount_fb33740e-69ab-4c16-9f3c-eda12265c1f7" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DerivativeLiabilityNotionalAmount"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_9dd171e3-0716-4992-8ece-0cd48a924e9d" xlink:to="loc_us-gaap_DerivativeLiabilityNotionalAmount_fb33740e-69ab-4c16-9f3c-eda12265c1f7" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DerivativeAverageFixedInterestRate_2c4c9830-ca22-436c-bb3f-455e744388b2" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DerivativeAverageFixedInterestRate"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_9dd171e3-0716-4992-8ece-0cd48a924e9d" xlink:to="loc_us-gaap_DerivativeAverageFixedInterestRate_2c4c9830-ca22-436c-bb3f-455e744388b2" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_InterestRateDerivativeNotDesignatedAsHedgingInstrumentsReceiveRate_000af274-6fee-425a-8a1c-f1c501af46b9" xlink:href="agnc-20220331.xsd#agnc_InterestRateDerivativeNotDesignatedAsHedgingInstrumentsReceiveRate"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_9dd171e3-0716-4992-8ece-0cd48a924e9d" xlink:to="loc_agnc_InterestRateDerivativeNotDesignatedAsHedgingInstrumentsReceiveRate_000af274-6fee-425a-8a1c-f1c501af46b9" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_OptionsAtCost_bedeb292-af48-4983-87bc-ca55320038d7" xlink:href="agnc-20220331.xsd#agnc_OptionsAtCost"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_9dd171e3-0716-4992-8ece-0cd48a924e9d" xlink:to="loc_agnc_OptionsAtCost_bedeb292-af48-4983-87bc-ca55320038d7" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_InterestRateDerivativesAtFairValueNet_f9157bd9-2df1-4318-b63b-e431e5aab69c" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_InterestRateDerivativesAtFairValueNet"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_9dd171e3-0716-4992-8ece-0cd48a924e9d" xlink:to="loc_us-gaap_InterestRateDerivativesAtFairValueNet_f9157bd9-2df1-4318-b63b-e431e5aab69c" xlink:type="arc" order="7"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_CashFlowHedgesDerivativeInstrumentsNotDesignatedAsHedgingInstrumentsAverageMonthsToExpiration_7f53fada-e214-4097-a61c-760bebc95869" xlink:href="agnc-20220331.xsd#agnc_CashFlowHedgesDerivativeInstrumentsNotDesignatedAsHedgingInstrumentsAverageMonthsToExpiration"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_9dd171e3-0716-4992-8ece-0cd48a924e9d" xlink:to="loc_agnc_CashFlowHedgesDerivativeInstrumentsNotDesignatedAsHedgingInstrumentsAverageMonthsToExpiration_7f53fada-e214-4097-a61c-760bebc95869" xlink:type="arc" order="8"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DerivativeAverageVariableInterestRate_36b16fb1-644b-4214-861d-5b0cf783d1c6" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DerivativeAverageVariableInterestRate"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_9dd171e3-0716-4992-8ece-0cd48a924e9d" xlink:to="loc_us-gaap_DerivativeAverageVariableInterestRate_36b16fb1-644b-4214-861d-5b0cf783d1c6" xlink:type="arc" order="9"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DerivativeAverageRemainingMaturity1_52d93654-00d4-48ad-bf24-8f337c39c8da" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DerivativeAverageRemainingMaturity1"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_9dd171e3-0716-4992-8ece-0cd48a924e9d" xlink:to="loc_us-gaap_DerivativeAverageRemainingMaturity1_52d93654-00d4-48ad-bf24-8f337c39c8da" xlink:type="arc" order="10"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_WeightedAverageForwardStartDate_592bd8f0-eacc-4ce7-b3ee-e5e3f8ce1676" xlink:href="agnc-20220331.xsd#agnc_WeightedAverageForwardStartDate"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_9dd171e3-0716-4992-8ece-0cd48a924e9d" xlink:to="loc_agnc_WeightedAverageForwardStartDate_592bd8f0-eacc-4ce7-b3ee-e5e3f8ce1676" xlink:type="arc" order="11"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_InterestRateSwapsLinkedto3MonthLIBOR_32c710c3-e263-4f9c-946c-931913270792" xlink:href="agnc-20220331.xsd#agnc_InterestRateSwapsLinkedto3MonthLIBOR"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_9dd171e3-0716-4992-8ece-0cd48a924e9d" xlink:to="loc_agnc_InterestRateSwapsLinkedto3MonthLIBOR_32c710c3-e263-4f9c-946c-931913270792" xlink:type="arc" order="12"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_InterestRateSwapsLinkedtoSecuredOvernightFinancingRate_a2d3cdea-b528-4562-a618-3a2e5f38dae4" xlink:href="agnc-20220331.xsd#agnc_InterestRateSwapsLinkedtoSecuredOvernightFinancingRate"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_9dd171e3-0716-4992-8ece-0cd48a924e9d" xlink:to="loc_agnc_InterestRateSwapsLinkedtoSecuredOvernightFinancingRate_a2d3cdea-b528-4562-a618-3a2e5f38dae4" xlink:type="arc" order="13"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DerivativeTable_99cc9a65-86ed-4ac5-8a67-be401b9aadc0" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DerivativeTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_StatementLineItems_9dd171e3-0716-4992-8ece-0cd48a924e9d" xlink:to="loc_us-gaap_DerivativeTable_99cc9a65-86ed-4ac5-8a67-be401b9aadc0" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_DerivativeInstrumentsDesignationAxis_b816c851-3150-44de-8af3-f6f9bde8c059" xlink:href="agnc-20220331.xsd#agnc_DerivativeInstrumentsDesignationAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_DerivativeTable_99cc9a65-86ed-4ac5-8a67-be401b9aadc0" xlink:to="loc_agnc_DerivativeInstrumentsDesignationAxis_b816c851-3150-44de-8af3-f6f9bde8c059" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_DerivativeInstrumentsDesignationDomain_b816c851-3150-44de-8af3-f6f9bde8c059_default" xlink:href="agnc-20220331.xsd#agnc_DerivativeInstrumentsDesignationDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_agnc_DerivativeInstrumentsDesignationAxis_b816c851-3150-44de-8af3-f6f9bde8c059" xlink:to="loc_agnc_DerivativeInstrumentsDesignationDomain_b816c851-3150-44de-8af3-f6f9bde8c059_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_DerivativeInstrumentsDesignationDomain_55c6788c-fab3-4817-a436-c7691c519952" xlink:href="agnc-20220331.xsd#agnc_DerivativeInstrumentsDesignationDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_agnc_DerivativeInstrumentsDesignationAxis_b816c851-3150-44de-8af3-f6f9bde8c059" xlink:to="loc_agnc_DerivativeInstrumentsDesignationDomain_55c6788c-fab3-4817-a436-c7691c519952" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncomeStatementLocationAxis_b3004dd2-3ced-4fa1-84a3-8b4e6a26ef5a" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_IncomeStatementLocationAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_DerivativeTable_99cc9a65-86ed-4ac5-8a67-be401b9aadc0" xlink:to="loc_us-gaap_IncomeStatementLocationAxis_b3004dd2-3ced-4fa1-84a3-8b4e6a26ef5a" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncomeStatementLocationDomain_b3004dd2-3ced-4fa1-84a3-8b4e6a26ef5a_default" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_IncomeStatementLocationDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_IncomeStatementLocationAxis_b3004dd2-3ced-4fa1-84a3-8b4e6a26ef5a" xlink:to="loc_us-gaap_IncomeStatementLocationDomain_b3004dd2-3ced-4fa1-84a3-8b4e6a26ef5a_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncomeStatementLocationDomain_2b4da30f-261b-4c84-a363-a5e4f2cece88" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_IncomeStatementLocationDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_IncomeStatementLocationAxis_b3004dd2-3ced-4fa1-84a3-8b4e6a26ef5a" xlink:to="loc_us-gaap_IncomeStatementLocationDomain_2b4da30f-261b-4c84-a363-a5e4f2cece88" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_InterestOnlyAndPrincipalOnlyStripMember_1beae322-b359-41c8-9674-8e9ce5f27a8c" xlink:href="agnc-20220331.xsd#agnc_InterestOnlyAndPrincipalOnlyStripMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncomeStatementLocationDomain_2b4da30f-261b-4c84-a363-a5e4f2cece88" xlink:to="loc_agnc_InterestOnlyAndPrincipalOnlyStripMember_1beae322-b359-41c8-9674-8e9ce5f27a8c" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_InvestmentTypeAxis_d230b4a2-f1e5-491f-b02a-9c157fe27abb" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_InvestmentTypeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_DerivativeTable_99cc9a65-86ed-4ac5-8a67-be401b9aadc0" xlink:to="loc_us-gaap_InvestmentTypeAxis_d230b4a2-f1e5-491f-b02a-9c157fe27abb" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_InvestmentTypeCategorizationMember_d230b4a2-f1e5-491f-b02a-9c157fe27abb_default" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_InvestmentTypeCategorizationMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_InvestmentTypeAxis_d230b4a2-f1e5-491f-b02a-9c157fe27abb" xlink:to="loc_us-gaap_InvestmentTypeCategorizationMember_d230b4a2-f1e5-491f-b02a-9c157fe27abb_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_InvestmentTypeCategorizationMember_c4fb137f-c224-484d-9768-590921d43336" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_InvestmentTypeCategorizationMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_InvestmentTypeAxis_d230b4a2-f1e5-491f-b02a-9c157fe27abb" xlink:to="loc_us-gaap_InvestmentTypeCategorizationMember_c4fb137f-c224-484d-9768-590921d43336" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_OtherDerivativesMember_d549aa9c-a308-4e05-8525-c93f1c05e1c3" xlink:href="agnc-20220331.xsd#agnc_OtherDerivativesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_InvestmentTypeCategorizationMember_c4fb137f-c224-484d-9768-590921d43336" xlink:to="loc_agnc_OtherDerivativesMember_d549aa9c-a308-4e05-8525-c93f1c05e1c3" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_DerivativesByMaturityAxis_1e6e58db-7f32-43cc-aebf-b4a3cc1659f2" xlink:href="agnc-20220331.xsd#agnc_DerivativesByMaturityAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_DerivativeTable_99cc9a65-86ed-4ac5-8a67-be401b9aadc0" xlink:to="loc_agnc_DerivativesByMaturityAxis_1e6e58db-7f32-43cc-aebf-b4a3cc1659f2" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_DerivativesByMaturityDomain_1e6e58db-7f32-43cc-aebf-b4a3cc1659f2_default" xlink:href="agnc-20220331.xsd#agnc_DerivativesByMaturityDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_agnc_DerivativesByMaturityAxis_1e6e58db-7f32-43cc-aebf-b4a3cc1659f2" xlink:to="loc_agnc_DerivativesByMaturityDomain_1e6e58db-7f32-43cc-aebf-b4a3cc1659f2_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_DerivativesByMaturityDomain_5bd83a68-966c-4209-9328-c19871b6496a" xlink:href="agnc-20220331.xsd#agnc_DerivativesByMaturityDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_agnc_DerivativesByMaturityAxis_1e6e58db-7f32-43cc-aebf-b4a3cc1659f2" xlink:to="loc_agnc_DerivativesByMaturityDomain_5bd83a68-966c-4209-9328-c19871b6496a" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_LessThanOrEqualToOneYearMember_5d9c1e2d-4f3c-46bf-8d54-c62453f503ab" xlink:href="agnc-20220331.xsd#agnc_LessThanOrEqualToOneYearMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_agnc_DerivativesByMaturityDomain_5bd83a68-966c-4209-9328-c19871b6496a" xlink:to="loc_agnc_LessThanOrEqualToOneYearMember_5d9c1e2d-4f3c-46bf-8d54-c62453f503ab" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_GreaterThanOneYearandLessThanorEqualtoTwoYearsMember_b9bc2ce0-11c6-4994-9bc5-9f5e666c36f1" xlink:href="agnc-20220331.xsd#agnc_GreaterThanOneYearandLessThanorEqualtoTwoYearsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_agnc_DerivativesByMaturityDomain_5bd83a68-966c-4209-9328-c19871b6496a" xlink:to="loc_agnc_GreaterThanOneYearandLessThanorEqualtoTwoYearsMember_b9bc2ce0-11c6-4994-9bc5-9f5e666c36f1" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_GreaterThanTwoYearsandLessThanorEqualtoThreeYearsMember_d4f42e02-a301-432a-9d05-e5fd5c914664" xlink:href="agnc-20220331.xsd#agnc_GreaterThanTwoYearsandLessThanorEqualtoThreeYearsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_agnc_DerivativesByMaturityDomain_5bd83a68-966c-4209-9328-c19871b6496a" xlink:to="loc_agnc_GreaterThanTwoYearsandLessThanorEqualtoThreeYearsMember_d4f42e02-a301-432a-9d05-e5fd5c914664" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_GreaterThanOneYearAndLessThanOrEqualToThreeYearsMember_65214671-420e-4273-b46c-28bee84ce713" xlink:href="agnc-20220331.xsd#agnc_GreaterThanOneYearAndLessThanOrEqualToThreeYearsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_agnc_DerivativesByMaturityDomain_5bd83a68-966c-4209-9328-c19871b6496a" xlink:to="loc_agnc_GreaterThanOneYearAndLessThanOrEqualToThreeYearsMember_65214671-420e-4273-b46c-28bee84ce713" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_GreaterThanThreeYearsAndLessThanOrEqualToFiveYearsMember_266990e0-3fac-44db-bdf3-1df84c89484b" xlink:href="agnc-20220331.xsd#agnc_GreaterThanThreeYearsAndLessThanOrEqualToFiveYearsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_agnc_DerivativesByMaturityDomain_5bd83a68-966c-4209-9328-c19871b6496a" xlink:to="loc_agnc_GreaterThanThreeYearsAndLessThanOrEqualToFiveYearsMember_266990e0-3fac-44db-bdf3-1df84c89484b" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_GreaterThanFiveYearsAndLessThanOrEqualToSevenYearsMember_20ab55c2-e19c-471e-bb5d-d187f0d87589" xlink:href="agnc-20220331.xsd#agnc_GreaterThanFiveYearsAndLessThanOrEqualToSevenYearsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_agnc_DerivativesByMaturityDomain_5bd83a68-966c-4209-9328-c19871b6496a" xlink:to="loc_agnc_GreaterThanFiveYearsAndLessThanOrEqualToSevenYearsMember_20ab55c2-e19c-471e-bb5d-d187f0d87589" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_GreaterThanSevenYearsAndLessThanOrEqualToTenYearsMember_7efe6f96-cf37-45b9-a5b2-71464f8874ed" xlink:href="agnc-20220331.xsd#agnc_GreaterThanSevenYearsAndLessThanOrEqualToTenYearsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_agnc_DerivativesByMaturityDomain_5bd83a68-966c-4209-9328-c19871b6496a" xlink:to="loc_agnc_GreaterThanSevenYearsAndLessThanOrEqualToTenYearsMember_7efe6f96-cf37-45b9-a5b2-71464f8874ed" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_GreaterThanTenYearsMember_803a0366-0405-45c0-b842-a377c72ea59d" xlink:href="agnc-20220331.xsd#agnc_GreaterThanTenYearsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_agnc_DerivativesByMaturityDomain_5bd83a68-966c-4209-9328-c19871b6496a" xlink:to="loc_agnc_GreaterThanTenYearsMember_803a0366-0405-45c0-b842-a377c72ea59d" xlink:type="arc" order="7"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_GreaterThanThreeYearsAndLessThanOrEqualToFourYearsMember_2848bd67-676d-405f-bd48-71e8a7e70b3d" xlink:href="agnc-20220331.xsd#agnc_GreaterThanThreeYearsAndLessThanOrEqualToFourYearsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_agnc_DerivativesByMaturityDomain_5bd83a68-966c-4209-9328-c19871b6496a" xlink:to="loc_agnc_GreaterThanThreeYearsAndLessThanOrEqualToFourYearsMember_2848bd67-676d-405f-bd48-71e8a7e70b3d" xlink:type="arc" order="8"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DerivativeInstrumentRiskAxis_8f59ee7f-b727-4d2f-88c3-8ade6f4c3224" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DerivativeInstrumentRiskAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_DerivativeTable_99cc9a65-86ed-4ac5-8a67-be401b9aadc0" xlink:to="loc_us-gaap_DerivativeInstrumentRiskAxis_8f59ee7f-b727-4d2f-88c3-8ade6f4c3224" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DerivativeContractTypeDomain_8f59ee7f-b727-4d2f-88c3-8ade6f4c3224_default" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DerivativeContractTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_DerivativeInstrumentRiskAxis_8f59ee7f-b727-4d2f-88c3-8ade6f4c3224" xlink:to="loc_us-gaap_DerivativeContractTypeDomain_8f59ee7f-b727-4d2f-88c3-8ade6f4c3224_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DerivativeContractTypeDomain_af795eab-ddb8-494f-b12e-f80975974638" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DerivativeContractTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_DerivativeInstrumentRiskAxis_8f59ee7f-b727-4d2f-88c3-8ade6f4c3224" xlink:to="loc_us-gaap_DerivativeContractTypeDomain_af795eab-ddb8-494f-b12e-f80975974638" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_PayerSwaptionMember_709a2dac-d22e-4d2d-a48a-458b212f3d0c" xlink:href="agnc-20220331.xsd#agnc_PayerSwaptionMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DerivativeContractTypeDomain_af795eab-ddb8-494f-b12e-f80975974638" xlink:to="loc_agnc_PayerSwaptionMember_709a2dac-d22e-4d2d-a48a-458b212f3d0c" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_InterestRateSwaptionMember_56b06dd2-43f7-46aa-90f0-4e0efa9a5f64" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_InterestRateSwaptionMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DerivativeContractTypeDomain_af795eab-ddb8-494f-b12e-f80975974638" xlink:to="loc_us-gaap_InterestRateSwaptionMember_56b06dd2-43f7-46aa-90f0-4e0efa9a5f64" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ForwardContractsMember_f5790f32-e2f8-4199-9f65-7b2fd40392b6" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ForwardContractsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DerivativeContractTypeDomain_af795eab-ddb8-494f-b12e-f80975974638" xlink:to="loc_us-gaap_ForwardContractsMember_f5790f32-e2f8-4199-9f65-7b2fd40392b6" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_InterestRateSwapsExcludingForwardStartingMember_84336163-203e-41d4-a643-800f1cfe04c0" xlink:href="agnc-20220331.xsd#agnc_InterestRateSwapsExcludingForwardStartingMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DerivativeContractTypeDomain_af795eab-ddb8-494f-b12e-f80975974638" xlink:to="loc_agnc_InterestRateSwapsExcludingForwardStartingMember_84336163-203e-41d4-a643-800f1cfe04c0" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_InterestRateSwapMember_2fda249d-7bc9-41cd-bc95-702fec6b8dcc" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_InterestRateSwapMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DerivativeContractTypeDomain_af795eab-ddb8-494f-b12e-f80975974638" xlink:to="loc_us-gaap_InterestRateSwapMember_2fda249d-7bc9-41cd-bc95-702fec6b8dcc" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_DerivativePositionAxis_1d87da0d-b17c-4932-ad24-b2cd565e24dd" xlink:href="agnc-20220331.xsd#agnc_DerivativePositionAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_DerivativeTable_99cc9a65-86ed-4ac5-8a67-be401b9aadc0" xlink:to="loc_agnc_DerivativePositionAxis_1d87da0d-b17c-4932-ad24-b2cd565e24dd" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_DerivativePositionDomain_1d87da0d-b17c-4932-ad24-b2cd565e24dd_default" xlink:href="agnc-20220331.xsd#agnc_DerivativePositionDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_agnc_DerivativePositionAxis_1d87da0d-b17c-4932-ad24-b2cd565e24dd" xlink:to="loc_agnc_DerivativePositionDomain_1d87da0d-b17c-4932-ad24-b2cd565e24dd_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_DerivativePositionDomain_eb0cc91e-a833-4f5b-814a-11aae8ca4de8" xlink:href="agnc-20220331.xsd#agnc_DerivativePositionDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_agnc_DerivativePositionAxis_1d87da0d-b17c-4932-ad24-b2cd565e24dd" xlink:to="loc_agnc_DerivativePositionDomain_eb0cc91e-a833-4f5b-814a-11aae8ca4de8" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_InterestRateSwapMember_701a6076-9cd3-4c3a-8e15-950e82d95501" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_InterestRateSwapMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_agnc_DerivativePositionDomain_eb0cc91e-a833-4f5b-814a-11aae8ca4de8" xlink:to="loc_us-gaap_InterestRateSwapMember_701a6076-9cd3-4c3a-8e15-950e82d95501" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DerivativeInstrumentRiskAxis_39aeac73-f559-44ed-bc98-68b9db652060" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DerivativeInstrumentRiskAxis"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DerivativeContractTypeDomain_39aeac73-f559-44ed-bc98-68b9db652060_default" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DerivativeContractTypeDomain"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.agnc.com/role/DerivativeandOtherHedgingInstrumentsRemainingInterestRateSwapTermDetails" xlink:type="simple" xlink:href="agnc-20220331.xsd#DerivativeandOtherHedgingInstrumentsRemainingInterestRateSwapTermDetails"/>
  <link:definitionLink xlink:role="http://www.agnc.com/role/DerivativeandOtherHedgingInstrumentsRemainingInterestRateSwapTermDetails" xlink:type="extended" id="i395419d256a645978bcd6458f238fada_DerivativeandOtherHedgingInstrumentsRemainingInterestRateSwapTermDetails">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StatementLineItems_09ce3d37-9475-4ea4-a779-3661303f3857" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_StatementLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_InterestRateSwapsLinkedto3MonthLIBOR_94123e61-25b5-4f57-a21d-5a1e949d4b04" xlink:href="agnc-20220331.xsd#agnc_InterestRateSwapsLinkedto3MonthLIBOR"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_09ce3d37-9475-4ea4-a779-3661303f3857" xlink:to="loc_agnc_InterestRateSwapsLinkedto3MonthLIBOR_94123e61-25b5-4f57-a21d-5a1e949d4b04" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_WeightedAverageForwardStartDate_d277b10d-b0d0-46f1-8e45-a2407bcb12cd" xlink:href="agnc-20220331.xsd#agnc_WeightedAverageForwardStartDate"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_09ce3d37-9475-4ea4-a779-3661303f3857" xlink:to="loc_agnc_WeightedAverageForwardStartDate_d277b10d-b0d0-46f1-8e45-a2407bcb12cd" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DerivativeInstrumentsNotDesignatedAsHedgingInstrumentsGainLossNet_136acadb-ef47-4cf1-b461-fc5c54d4cc1d" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DerivativeInstrumentsNotDesignatedAsHedgingInstrumentsGainLossNet"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_09ce3d37-9475-4ea4-a779-3661303f3857" xlink:to="loc_us-gaap_DerivativeInstrumentsNotDesignatedAsHedgingInstrumentsGainLossNet_136acadb-ef47-4cf1-b461-fc5c54d4cc1d" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_OptionsAtCost_64084b3b-9c04-4ac3-88bb-9b084a358345" xlink:href="agnc-20220331.xsd#agnc_OptionsAtCost"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_09ce3d37-9475-4ea4-a779-3661303f3857" xlink:to="loc_agnc_OptionsAtCost_64084b3b-9c04-4ac3-88bb-9b084a358345" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_InterestRateDerivativesAtFairValueNet_89b108b1-edcb-40ad-a634-9eed808c4dad" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_InterestRateDerivativesAtFairValueNet"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_09ce3d37-9475-4ea4-a779-3661303f3857" xlink:to="loc_us-gaap_InterestRateDerivativesAtFairValueNet_89b108b1-edcb-40ad-a634-9eed808c4dad" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_CashFlowHedgesDerivativeInstrumentsNotDesignatedAsHedgingInstrumentsAverageMonthsToExpiration_e9bc9277-6bb8-4c80-9323-53f534855b87" xlink:href="agnc-20220331.xsd#agnc_CashFlowHedgesDerivativeInstrumentsNotDesignatedAsHedgingInstrumentsAverageMonthsToExpiration"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_09ce3d37-9475-4ea4-a779-3661303f3857" xlink:to="loc_agnc_CashFlowHedgesDerivativeInstrumentsNotDesignatedAsHedgingInstrumentsAverageMonthsToExpiration_e9bc9277-6bb8-4c80-9323-53f534855b87" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DerivativeLiabilityNotionalAmount_9292a27f-d36c-4bdb-98fc-4329f84b70ca" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DerivativeLiabilityNotionalAmount"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_09ce3d37-9475-4ea4-a779-3661303f3857" xlink:to="loc_us-gaap_DerivativeLiabilityNotionalAmount_9292a27f-d36c-4bdb-98fc-4329f84b70ca" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DerivativeAverageFixedInterestRate_6a05a4ec-8f4d-44d6-9e3f-23a65d28bda1" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DerivativeAverageFixedInterestRate"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_09ce3d37-9475-4ea4-a779-3661303f3857" xlink:to="loc_us-gaap_DerivativeAverageFixedInterestRate_6a05a4ec-8f4d-44d6-9e3f-23a65d28bda1" xlink:type="arc" order="7"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_InterestRateDerivativeNotDesignatedAsHedgingInstrumentsReceiveRate_8947664e-715d-4b08-8aa7-9dfb89676095" xlink:href="agnc-20220331.xsd#agnc_InterestRateDerivativeNotDesignatedAsHedgingInstrumentsReceiveRate"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_09ce3d37-9475-4ea4-a779-3661303f3857" xlink:to="loc_agnc_InterestRateDerivativeNotDesignatedAsHedgingInstrumentsReceiveRate_8947664e-715d-4b08-8aa7-9dfb89676095" xlink:type="arc" order="8"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DerivativeAverageRemainingMaturity1_0ccf2d68-75e5-4b97-9177-aea4a8554d26" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DerivativeAverageRemainingMaturity1"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_09ce3d37-9475-4ea4-a779-3661303f3857" xlink:to="loc_us-gaap_DerivativeAverageRemainingMaturity1_0ccf2d68-75e5-4b97-9177-aea4a8554d26" xlink:type="arc" order="9"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_InterestRateSwapsLinkedtoOvernightIndexSwapRate_7196f6e9-e8f4-481b-b183-548750e76cc7" xlink:href="agnc-20220331.xsd#agnc_InterestRateSwapsLinkedtoOvernightIndexSwapRate"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_09ce3d37-9475-4ea4-a779-3661303f3857" xlink:to="loc_agnc_InterestRateSwapsLinkedtoOvernightIndexSwapRate_7196f6e9-e8f4-481b-b183-548750e76cc7" xlink:type="arc" order="10"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DerivativeTable_6b16deb0-7989-42ec-bcf3-95cc8eae1715" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DerivativeTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_StatementLineItems_09ce3d37-9475-4ea4-a779-3661303f3857" xlink:to="loc_us-gaap_DerivativeTable_6b16deb0-7989-42ec-bcf3-95cc8eae1715" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_DerivativePositionAxis_63d8e2d9-f298-4d7a-b160-0d85ebbb48f4" xlink:href="agnc-20220331.xsd#agnc_DerivativePositionAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_DerivativeTable_6b16deb0-7989-42ec-bcf3-95cc8eae1715" xlink:to="loc_agnc_DerivativePositionAxis_63d8e2d9-f298-4d7a-b160-0d85ebbb48f4" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_DerivativePositionDomain_63d8e2d9-f298-4d7a-b160-0d85ebbb48f4_default" xlink:href="agnc-20220331.xsd#agnc_DerivativePositionDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_agnc_DerivativePositionAxis_63d8e2d9-f298-4d7a-b160-0d85ebbb48f4" xlink:to="loc_agnc_DerivativePositionDomain_63d8e2d9-f298-4d7a-b160-0d85ebbb48f4_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_DerivativePositionDomain_ce67d2ff-08e1-4ba7-9e42-8072e592a497" xlink:href="agnc-20220331.xsd#agnc_DerivativePositionDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_agnc_DerivativePositionAxis_63d8e2d9-f298-4d7a-b160-0d85ebbb48f4" xlink:to="loc_agnc_DerivativePositionDomain_ce67d2ff-08e1-4ba7-9e42-8072e592a497" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_DerivativeInstrumentsDesignationAxis_3103892f-0f80-41d3-b78a-5b9e0854db74" xlink:href="agnc-20220331.xsd#agnc_DerivativeInstrumentsDesignationAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_DerivativeTable_6b16deb0-7989-42ec-bcf3-95cc8eae1715" xlink:to="loc_agnc_DerivativeInstrumentsDesignationAxis_3103892f-0f80-41d3-b78a-5b9e0854db74" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_DerivativeInstrumentsDesignationDomain_3103892f-0f80-41d3-b78a-5b9e0854db74_default" xlink:href="agnc-20220331.xsd#agnc_DerivativeInstrumentsDesignationDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_agnc_DerivativeInstrumentsDesignationAxis_3103892f-0f80-41d3-b78a-5b9e0854db74" xlink:to="loc_agnc_DerivativeInstrumentsDesignationDomain_3103892f-0f80-41d3-b78a-5b9e0854db74_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_DerivativeInstrumentsDesignationDomain_d3aa7277-1dac-4b81-bc4d-3a72f8998fa2" xlink:href="agnc-20220331.xsd#agnc_DerivativeInstrumentsDesignationDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_agnc_DerivativeInstrumentsDesignationAxis_3103892f-0f80-41d3-b78a-5b9e0854db74" xlink:to="loc_agnc_DerivativeInstrumentsDesignationDomain_d3aa7277-1dac-4b81-bc4d-3a72f8998fa2" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_InterestRateSwapsExcludingForwardStartingMember_2faa4ff5-5fce-4055-a4d6-6582e63fe293" xlink:href="agnc-20220331.xsd#agnc_InterestRateSwapsExcludingForwardStartingMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_agnc_DerivativeInstrumentsDesignationDomain_d3aa7277-1dac-4b81-bc4d-3a72f8998fa2" xlink:to="loc_agnc_InterestRateSwapsExcludingForwardStartingMember_2faa4ff5-5fce-4055-a4d6-6582e63fe293" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncomeStatementLocationAxis_c893efaf-729e-42cc-a61a-bb6acbefa22c" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_IncomeStatementLocationAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_DerivativeTable_6b16deb0-7989-42ec-bcf3-95cc8eae1715" xlink:to="loc_us-gaap_IncomeStatementLocationAxis_c893efaf-729e-42cc-a61a-bb6acbefa22c" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncomeStatementLocationDomain_c893efaf-729e-42cc-a61a-bb6acbefa22c_default" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_IncomeStatementLocationDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_IncomeStatementLocationAxis_c893efaf-729e-42cc-a61a-bb6acbefa22c" xlink:to="loc_us-gaap_IncomeStatementLocationDomain_c893efaf-729e-42cc-a61a-bb6acbefa22c_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncomeStatementLocationDomain_cc84e551-8f0d-4d22-b50e-e3c2e19d48a4" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_IncomeStatementLocationDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_IncomeStatementLocationAxis_c893efaf-729e-42cc-a61a-bb6acbefa22c" xlink:to="loc_us-gaap_IncomeStatementLocationDomain_cc84e551-8f0d-4d22-b50e-e3c2e19d48a4" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_InterestOnlyAndPrincipalOnlyStripMember_a654dd21-ba50-4b38-a805-d67a8af23584" xlink:href="agnc-20220331.xsd#agnc_InterestOnlyAndPrincipalOnlyStripMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncomeStatementLocationDomain_cc84e551-8f0d-4d22-b50e-e3c2e19d48a4" xlink:to="loc_agnc_InterestOnlyAndPrincipalOnlyStripMember_a654dd21-ba50-4b38-a805-d67a8af23584" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_InvestmentTypeAxis_0ba22542-119d-4381-b648-2c5af0ab6652" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_InvestmentTypeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_DerivativeTable_6b16deb0-7989-42ec-bcf3-95cc8eae1715" xlink:to="loc_us-gaap_InvestmentTypeAxis_0ba22542-119d-4381-b648-2c5af0ab6652" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_InvestmentTypeCategorizationMember_0ba22542-119d-4381-b648-2c5af0ab6652_default" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_InvestmentTypeCategorizationMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_InvestmentTypeAxis_0ba22542-119d-4381-b648-2c5af0ab6652" xlink:to="loc_us-gaap_InvestmentTypeCategorizationMember_0ba22542-119d-4381-b648-2c5af0ab6652_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_InvestmentTypeCategorizationMember_a4fb0727-3817-4435-a30f-9cbd2e15bc67" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_InvestmentTypeCategorizationMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_InvestmentTypeAxis_0ba22542-119d-4381-b648-2c5af0ab6652" xlink:to="loc_us-gaap_InvestmentTypeCategorizationMember_a4fb0727-3817-4435-a30f-9cbd2e15bc67" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_BermudanMember_0a9d4ffc-2dff-4639-bc6c-4a3b09daf95f" xlink:href="agnc-20220331.xsd#agnc_BermudanMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_InvestmentTypeCategorizationMember_a4fb0727-3817-4435-a30f-9cbd2e15bc67" xlink:to="loc_agnc_BermudanMember_0a9d4ffc-2dff-4639-bc6c-4a3b09daf95f" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_OtherDerivativesMember_d600fbd9-7c67-49fa-9c49-3a21bee7c95f" xlink:href="agnc-20220331.xsd#agnc_OtherDerivativesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_InvestmentTypeCategorizationMember_a4fb0727-3817-4435-a30f-9cbd2e15bc67" xlink:to="loc_agnc_OtherDerivativesMember_d600fbd9-7c67-49fa-9c49-3a21bee7c95f" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_DerivativesByMaturityAxis_678c2b2e-2bd2-4053-9a7f-fdfa48026a09" xlink:href="agnc-20220331.xsd#agnc_DerivativesByMaturityAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_DerivativeTable_6b16deb0-7989-42ec-bcf3-95cc8eae1715" xlink:to="loc_agnc_DerivativesByMaturityAxis_678c2b2e-2bd2-4053-9a7f-fdfa48026a09" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_DerivativesByMaturityDomain_678c2b2e-2bd2-4053-9a7f-fdfa48026a09_default" xlink:href="agnc-20220331.xsd#agnc_DerivativesByMaturityDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_agnc_DerivativesByMaturityAxis_678c2b2e-2bd2-4053-9a7f-fdfa48026a09" xlink:to="loc_agnc_DerivativesByMaturityDomain_678c2b2e-2bd2-4053-9a7f-fdfa48026a09_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_DerivativesByMaturityDomain_f83b579b-d1bf-42a8-a5c8-f89a5176d61f" xlink:href="agnc-20220331.xsd#agnc_DerivativesByMaturityDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_agnc_DerivativesByMaturityAxis_678c2b2e-2bd2-4053-9a7f-fdfa48026a09" xlink:to="loc_agnc_DerivativesByMaturityDomain_f83b579b-d1bf-42a8-a5c8-f89a5176d61f" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_LessThanOrEqualToOneYearMember_2e840085-a4f7-4d9e-a8d2-481fd981de5f" xlink:href="agnc-20220331.xsd#agnc_LessThanOrEqualToOneYearMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_agnc_DerivativesByMaturityDomain_f83b579b-d1bf-42a8-a5c8-f89a5176d61f" xlink:to="loc_agnc_LessThanOrEqualToOneYearMember_2e840085-a4f7-4d9e-a8d2-481fd981de5f" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_GreaterThanOneYearAndLessThanOrEqualToThreeYearsMember_3a7e590a-cc2d-407e-a4ea-5d711c96dbe8" xlink:href="agnc-20220331.xsd#agnc_GreaterThanOneYearAndLessThanOrEqualToThreeYearsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_agnc_DerivativesByMaturityDomain_f83b579b-d1bf-42a8-a5c8-f89a5176d61f" xlink:to="loc_agnc_GreaterThanOneYearAndLessThanOrEqualToThreeYearsMember_3a7e590a-cc2d-407e-a4ea-5d711c96dbe8" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DerivativeInstrumentRiskAxis_7d83eda9-bc8d-42eb-afd5-79fa804b296f" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DerivativeInstrumentRiskAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_DerivativeTable_6b16deb0-7989-42ec-bcf3-95cc8eae1715" xlink:to="loc_us-gaap_DerivativeInstrumentRiskAxis_7d83eda9-bc8d-42eb-afd5-79fa804b296f" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DerivativeContractTypeDomain_7d83eda9-bc8d-42eb-afd5-79fa804b296f_default" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DerivativeContractTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_DerivativeInstrumentRiskAxis_7d83eda9-bc8d-42eb-afd5-79fa804b296f" xlink:to="loc_us-gaap_DerivativeContractTypeDomain_7d83eda9-bc8d-42eb-afd5-79fa804b296f_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DerivativeContractTypeDomain_fae799d1-4be5-44b1-bf87-5036b7348ca1" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DerivativeContractTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_DerivativeInstrumentRiskAxis_7d83eda9-bc8d-42eb-afd5-79fa804b296f" xlink:to="loc_us-gaap_DerivativeContractTypeDomain_fae799d1-4be5-44b1-bf87-5036b7348ca1" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ForwardContractsMember_91e6799f-1670-4d39-8e22-2c94d7c25803" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ForwardContractsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DerivativeContractTypeDomain_fae799d1-4be5-44b1-bf87-5036b7348ca1" xlink:to="loc_us-gaap_ForwardContractsMember_91e6799f-1670-4d39-8e22-2c94d7c25803" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_InterestRateSwaptionMember_d282ee02-610c-4c8d-a5b0-d2f859ae745a" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_InterestRateSwaptionMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DerivativeContractTypeDomain_fae799d1-4be5-44b1-bf87-5036b7348ca1" xlink:to="loc_us-gaap_InterestRateSwaptionMember_d282ee02-610c-4c8d-a5b0-d2f859ae745a" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_PayerSwaptionMember_550ab2cc-0f41-475e-8cae-ae663d72fe1a" xlink:href="agnc-20220331.xsd#agnc_PayerSwaptionMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DerivativeContractTypeDomain_fae799d1-4be5-44b1-bf87-5036b7348ca1" xlink:to="loc_agnc_PayerSwaptionMember_550ab2cc-0f41-475e-8cae-ae663d72fe1a" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_InterestRateSwapMember_dde60aca-e38f-40cd-8fbf-ac0da0a2a338" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_InterestRateSwapMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DerivativeContractTypeDomain_fae799d1-4be5-44b1-bf87-5036b7348ca1" xlink:to="loc_us-gaap_InterestRateSwapMember_dde60aca-e38f-40cd-8fbf-ac0da0a2a338" xlink:type="arc" order="3"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.agnc.com/role/DerivativeandOtherHedgingInstrumentsUSTreasurySecuritiesDetails" xlink:type="simple" xlink:href="agnc-20220331.xsd#DerivativeandOtherHedgingInstrumentsUSTreasurySecuritiesDetails"/>
  <link:definitionLink xlink:role="http://www.agnc.com/role/DerivativeandOtherHedgingInstrumentsUSTreasurySecuritiesDetails" xlink:type="extended" id="i5f2c6aa0d715440092a28f6f4dca75e3_DerivativeandOtherHedgingInstrumentsUSTreasurySecuritiesDetails">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DerivativeLineItems_a2897952-7652-4e47-bfd7-b7c79990d237" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DerivativeLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DerivativeNotionalAmount_1d7772a6-6c04-4dcf-95a8-c4fe5dd026fb" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DerivativeNotionalAmount"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DerivativeLineItems_a2897952-7652-4e47-bfd7-b7c79990d237" xlink:to="loc_us-gaap_DerivativeNotionalAmount_1d7772a6-6c04-4dcf-95a8-c4fe5dd026fb" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_DerivativeForwardSettlementValue_f59b4f2b-26b1-4425-9b6b-e8294d48e34b" xlink:href="agnc-20220331.xsd#agnc_DerivativeForwardSettlementValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DerivativeLineItems_a2897952-7652-4e47-bfd7-b7c79990d237" xlink:to="loc_agnc_DerivativeForwardSettlementValue_f59b4f2b-26b1-4425-9b6b-e8294d48e34b" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DerivativeFairValueOfDerivativeAsset_9f2f2da6-bb33-423a-b47c-1e60a35c95f5" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DerivativeFairValueOfDerivativeAsset"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DerivativeLineItems_a2897952-7652-4e47-bfd7-b7c79990d237" xlink:to="loc_us-gaap_DerivativeFairValueOfDerivativeAsset_9f2f2da6-bb33-423a-b47c-1e60a35c95f5" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DerivativeFairValueOfDerivativeNet_193f20d8-bd76-4aac-8b7d-1140afaf6fd8" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DerivativeFairValueOfDerivativeNet"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DerivativeLineItems_a2897952-7652-4e47-bfd7-b7c79990d237" xlink:to="loc_us-gaap_DerivativeFairValueOfDerivativeNet_193f20d8-bd76-4aac-8b7d-1140afaf6fd8" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_Governmentbondsownedandsoldshortnet_5f18f535-bb9e-4a85-8f73-9ed51bcf5a29" xlink:href="agnc-20220331.xsd#agnc_Governmentbondsownedandsoldshortnet"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DerivativeLineItems_a2897952-7652-4e47-bfd7-b7c79990d237" xlink:to="loc_agnc_Governmentbondsownedandsoldshortnet_5f18f535-bb9e-4a85-8f73-9ed51bcf5a29" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_WeightedAverageYieldPercentage_6ac3ada2-1d39-4871-bac2-e95b574f0f70" xlink:href="agnc-20220331.xsd#agnc_WeightedAverageYieldPercentage"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DerivativeLineItems_a2897952-7652-4e47-bfd7-b7c79990d237" xlink:to="loc_agnc_WeightedAverageYieldPercentage_6ac3ada2-1d39-4871-bac2-e95b574f0f70" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DerivativeTable_df3bb4b9-04eb-42d9-a0ed-ab4edbc85d68" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DerivativeTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_DerivativeLineItems_a2897952-7652-4e47-bfd7-b7c79990d237" xlink:to="loc_us-gaap_DerivativeTable_df3bb4b9-04eb-42d9-a0ed-ab4edbc85d68" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_InvestmentTypeAxis_22204778-f183-493b-8123-f1ba47b540d0" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_InvestmentTypeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_DerivativeTable_df3bb4b9-04eb-42d9-a0ed-ab4edbc85d68" xlink:to="loc_us-gaap_InvestmentTypeAxis_22204778-f183-493b-8123-f1ba47b540d0" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_InvestmentTypeCategorizationMember_22204778-f183-493b-8123-f1ba47b540d0_default" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_InvestmentTypeCategorizationMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_InvestmentTypeAxis_22204778-f183-493b-8123-f1ba47b540d0" xlink:to="loc_us-gaap_InvestmentTypeCategorizationMember_22204778-f183-493b-8123-f1ba47b540d0_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_InvestmentTypeCategorizationMember_883adbcd-927e-45c4-b3dc-9efcba902274" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_InvestmentTypeCategorizationMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_InvestmentTypeAxis_22204778-f183-493b-8123-f1ba47b540d0" xlink:to="loc_us-gaap_InvestmentTypeCategorizationMember_883adbcd-927e-45c4-b3dc-9efcba902274" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_USTreasurySecuritiesMember_a86257df-7f7c-4756-ab6b-7597f39375f6" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_USTreasurySecuritiesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_InvestmentTypeCategorizationMember_883adbcd-927e-45c4-b3dc-9efcba902274" xlink:to="loc_us-gaap_USTreasurySecuritiesMember_a86257df-7f7c-4756-ab6b-7597f39375f6" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_DerivativeInstrumentsDesignationAxis_9505a12b-07ff-4201-85a6-49338b9183f8" xlink:href="agnc-20220331.xsd#agnc_DerivativeInstrumentsDesignationAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_DerivativeTable_df3bb4b9-04eb-42d9-a0ed-ab4edbc85d68" xlink:to="loc_agnc_DerivativeInstrumentsDesignationAxis_9505a12b-07ff-4201-85a6-49338b9183f8" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_DerivativeInstrumentsDesignationDomain_9505a12b-07ff-4201-85a6-49338b9183f8_default" xlink:href="agnc-20220331.xsd#agnc_DerivativeInstrumentsDesignationDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_agnc_DerivativeInstrumentsDesignationAxis_9505a12b-07ff-4201-85a6-49338b9183f8" xlink:to="loc_agnc_DerivativeInstrumentsDesignationDomain_9505a12b-07ff-4201-85a6-49338b9183f8_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_DerivativeInstrumentsDesignationDomain_a0d55541-f33a-4d87-bcdf-82b7c6f1dae9" xlink:href="agnc-20220331.xsd#agnc_DerivativeInstrumentsDesignationDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_agnc_DerivativeInstrumentsDesignationAxis_9505a12b-07ff-4201-85a6-49338b9183f8" xlink:to="loc_agnc_DerivativeInstrumentsDesignationDomain_a0d55541-f33a-4d87-bcdf-82b7c6f1dae9" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_AtCostBasisMember_4974c1b5-bb3a-43a9-877d-e42957fbab86" xlink:href="agnc-20220331.xsd#agnc_AtCostBasisMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_agnc_DerivativeInstrumentsDesignationDomain_a0d55541-f33a-4d87-bcdf-82b7c6f1dae9" xlink:to="loc_agnc_AtCostBasisMember_4974c1b5-bb3a-43a9-877d-e42957fbab86" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DerivativeInstrumentsGainLossByHedgingRelationshipAxis_10e994c5-f4f7-407b-928c-e2fda7b403f4" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DerivativeInstrumentsGainLossByHedgingRelationshipAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_DerivativeTable_df3bb4b9-04eb-42d9-a0ed-ab4edbc85d68" xlink:to="loc_us-gaap_DerivativeInstrumentsGainLossByHedgingRelationshipAxis_10e994c5-f4f7-407b-928c-e2fda7b403f4" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_HedgingRelationshipDomain_10e994c5-f4f7-407b-928c-e2fda7b403f4_default" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_HedgingRelationshipDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_DerivativeInstrumentsGainLossByHedgingRelationshipAxis_10e994c5-f4f7-407b-928c-e2fda7b403f4" xlink:to="loc_us-gaap_HedgingRelationshipDomain_10e994c5-f4f7-407b-928c-e2fda7b403f4_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_HedgingRelationshipDomain_618d4bc7-2d4a-49d4-84b3-975dfd26e7c3" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_HedgingRelationshipDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_DerivativeInstrumentsGainLossByHedgingRelationshipAxis_10e994c5-f4f7-407b-928c-e2fda7b403f4" xlink:to="loc_us-gaap_HedgingRelationshipDomain_618d4bc7-2d4a-49d4-84b3-975dfd26e7c3" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueHedgingMember_b330f27d-5deb-4858-93ff-1d6f76b98be7" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FairValueHedgingMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_HedgingRelationshipDomain_618d4bc7-2d4a-49d4-84b3-975dfd26e7c3" xlink:to="loc_us-gaap_FairValueHedgingMember_b330f27d-5deb-4858-93ff-1d6f76b98be7" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PositionAxis_8a7497e8-9e8c-4eb9-a99f-4c0ba3d6b52c" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_PositionAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_DerivativeTable_df3bb4b9-04eb-42d9-a0ed-ab4edbc85d68" xlink:to="loc_us-gaap_PositionAxis_8a7497e8-9e8c-4eb9-a99f-4c0ba3d6b52c" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PositionDomain_8a7497e8-9e8c-4eb9-a99f-4c0ba3d6b52c_default" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_PositionDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_PositionAxis_8a7497e8-9e8c-4eb9-a99f-4c0ba3d6b52c" xlink:to="loc_us-gaap_PositionDomain_8a7497e8-9e8c-4eb9-a99f-4c0ba3d6b52c_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PositionDomain_e1e73267-eaba-4c3a-b7b7-6a2affb303c3" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_PositionDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_PositionAxis_8a7497e8-9e8c-4eb9-a99f-4c0ba3d6b52c" xlink:to="loc_us-gaap_PositionDomain_e1e73267-eaba-4c3a-b7b7-6a2affb303c3" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShortMember_835f2abc-bbc4-4e93-9dc9-766b8bd9603d" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShortMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PositionDomain_e1e73267-eaba-4c3a-b7b7-6a2affb303c3" xlink:to="loc_us-gaap_ShortMember_835f2abc-bbc4-4e93-9dc9-766b8bd9603d" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LongMember_98ba7e49-22c2-4caf-853b-19fec5a7efc4" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_LongMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PositionDomain_e1e73267-eaba-4c3a-b7b7-6a2affb303c3" xlink:to="loc_us-gaap_LongMember_98ba7e49-22c2-4caf-853b-19fec5a7efc4" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_DerivativesByMaturityAxis_7a886e70-078f-439d-a16c-86a37baecf29" xlink:href="agnc-20220331.xsd#agnc_DerivativesByMaturityAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_DerivativeTable_df3bb4b9-04eb-42d9-a0ed-ab4edbc85d68" xlink:to="loc_agnc_DerivativesByMaturityAxis_7a886e70-078f-439d-a16c-86a37baecf29" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_DerivativesByMaturityDomain_7a886e70-078f-439d-a16c-86a37baecf29_default" xlink:href="agnc-20220331.xsd#agnc_DerivativesByMaturityDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_agnc_DerivativesByMaturityAxis_7a886e70-078f-439d-a16c-86a37baecf29" xlink:to="loc_agnc_DerivativesByMaturityDomain_7a886e70-078f-439d-a16c-86a37baecf29_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_DerivativesByMaturityDomain_39fb080d-fb96-411c-b765-4996290c3c3f" xlink:href="agnc-20220331.xsd#agnc_DerivativesByMaturityDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_agnc_DerivativesByMaturityAxis_7a886e70-078f-439d-a16c-86a37baecf29" xlink:to="loc_agnc_DerivativesByMaturityDomain_39fb080d-fb96-411c-b765-4996290c3c3f" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_A10YearMaturityMember_255ef58d-89e1-4a8b-bd76-690d0c637361" xlink:href="agnc-20220331.xsd#agnc_A10YearMaturityMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_agnc_DerivativesByMaturityDomain_39fb080d-fb96-411c-b765-4996290c3c3f" xlink:to="loc_agnc_A10YearMaturityMember_255ef58d-89e1-4a8b-bd76-690d0c637361" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_A5YearMaturityMember_06e0fc94-3de1-47bd-a4fe-a72d1200d7ba" xlink:href="agnc-20220331.xsd#agnc_A5YearMaturityMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_agnc_DerivativesByMaturityDomain_39fb080d-fb96-411c-b765-4996290c3c3f" xlink:to="loc_agnc_A5YearMaturityMember_06e0fc94-3de1-47bd-a4fe-a72d1200d7ba" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_DerivativePositionAxis_05f761ec-ad51-4a6d-a54b-b9abc867074c" xlink:href="agnc-20220331.xsd#agnc_DerivativePositionAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_DerivativeTable_df3bb4b9-04eb-42d9-a0ed-ab4edbc85d68" xlink:to="loc_agnc_DerivativePositionAxis_05f761ec-ad51-4a6d-a54b-b9abc867074c" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_DerivativePositionDomain_05f761ec-ad51-4a6d-a54b-b9abc867074c_default" xlink:href="agnc-20220331.xsd#agnc_DerivativePositionDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_agnc_DerivativePositionAxis_05f761ec-ad51-4a6d-a54b-b9abc867074c" xlink:to="loc_agnc_DerivativePositionDomain_05f761ec-ad51-4a6d-a54b-b9abc867074c_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_DerivativePositionDomain_1aa68aa1-7833-41d3-a5df-3ec5fe25b4da" xlink:href="agnc-20220331.xsd#agnc_DerivativePositionDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_agnc_DerivativePositionAxis_05f761ec-ad51-4a6d-a54b-b9abc867074c" xlink:to="loc_agnc_DerivativePositionDomain_1aa68aa1-7833-41d3-a5df-3ec5fe25b4da" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_A2.5CouponMember_d438bd91-f21b-41db-9e3d-90502078f185" xlink:href="agnc-20220331.xsd#agnc_A2.5CouponMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_agnc_DerivativePositionDomain_1aa68aa1-7833-41d3-a5df-3ec5fe25b4da" xlink:to="loc_agnc_A2.5CouponMember_d438bd91-f21b-41db-9e3d-90502078f185" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DerivativeInstrumentRiskAxis_dff3ff4d-5f5e-4707-95bf-299e6849d132" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DerivativeInstrumentRiskAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_DerivativeTable_df3bb4b9-04eb-42d9-a0ed-ab4edbc85d68" xlink:to="loc_us-gaap_DerivativeInstrumentRiskAxis_dff3ff4d-5f5e-4707-95bf-299e6849d132" xlink:type="arc" order="7"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DerivativeContractTypeDomain_dff3ff4d-5f5e-4707-95bf-299e6849d132_default" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DerivativeContractTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_DerivativeInstrumentRiskAxis_dff3ff4d-5f5e-4707-95bf-299e6849d132" xlink:to="loc_us-gaap_DerivativeContractTypeDomain_dff3ff4d-5f5e-4707-95bf-299e6849d132_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DerivativeContractTypeDomain_0b6b441e-9498-4851-aa73-a9887f1a917c" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DerivativeContractTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_DerivativeInstrumentRiskAxis_dff3ff4d-5f5e-4707-95bf-299e6849d132" xlink:to="loc_us-gaap_DerivativeContractTypeDomain_0b6b441e-9498-4851-aa73-a9887f1a917c" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_A7YearsMaturityMember_51ecee77-70c8-4bb4-844e-a5366f8986ca" xlink:href="agnc-20220331.xsd#agnc_A7YearsMaturityMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DerivativeContractTypeDomain_0b6b441e-9498-4851-aa73-a9887f1a917c" xlink:to="loc_agnc_A7YearsMaturityMember_51ecee77-70c8-4bb4-844e-a5366f8986ca" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FutureMember_1d5be61f-ce73-4d1d-828f-bfe2446afd3e" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FutureMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DerivativeContractTypeDomain_0b6b441e-9498-4851-aa73-a9887f1a917c" xlink:to="loc_us-gaap_FutureMember_1d5be61f-ce73-4d1d-828f-bfe2446afd3e" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_A15YearMaturityMember_b83ac99a-be46-4fe9-982e-f832d3dcb179" xlink:href="agnc-20220331.xsd#agnc_A15YearMaturityMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DerivativeContractTypeDomain_0b6b441e-9498-4851-aa73-a9887f1a917c" xlink:to="loc_agnc_A15YearMaturityMember_b83ac99a-be46-4fe9-982e-f832d3dcb179" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_AtParValueMember_af9b02e0-6071-4b8f-aac9-1081362352a4" xlink:href="agnc-20220331.xsd#agnc_AtParValueMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DerivativeContractTypeDomain_0b6b441e-9498-4851-aa73-a9887f1a917c" xlink:to="loc_agnc_AtParValueMember_af9b02e0-6071-4b8f-aac9-1081362352a4" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_AtCostBasisMember_048b2886-440e-4840-8c05-3060a35e6244" xlink:href="agnc-20220331.xsd#agnc_AtCostBasisMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DerivativeContractTypeDomain_0b6b441e-9498-4851-aa73-a9887f1a917c" xlink:to="loc_agnc_AtCostBasisMember_048b2886-440e-4840-8c05-3060a35e6244" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_USTreasurySecuritiesMember_bef30d45-47ad-4046-8299-a4bb1485e56d" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_USTreasurySecuritiesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DerivativeContractTypeDomain_0b6b441e-9498-4851-aa73-a9887f1a917c" xlink:to="loc_us-gaap_USTreasurySecuritiesMember_bef30d45-47ad-4046-8299-a4bb1485e56d" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_TBAAndForwardSettlingSecuritiesMember_50f7eacf-4457-449d-bce5-5b3fa08e85c1" xlink:href="agnc-20220331.xsd#agnc_TBAAndForwardSettlingSecuritiesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DerivativeContractTypeDomain_0b6b441e-9498-4851-aa73-a9887f1a917c" xlink:to="loc_agnc_TBAAndForwardSettlingSecuritiesMember_50f7eacf-4457-449d-bce5-5b3fa08e85c1" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_A5YearMaturityMember_683fdaeb-81d4-44f6-a0b4-483b9acae931" xlink:href="agnc-20220331.xsd#agnc_A5YearMaturityMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DerivativeContractTypeDomain_0b6b441e-9498-4851-aa73-a9887f1a917c" xlink:to="loc_agnc_A5YearMaturityMember_683fdaeb-81d4-44f6-a0b4-483b9acae931" xlink:type="arc" order="7"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_A10YearMaturityMember_8b007cf4-f2ed-40c4-9e84-8a25554ae338" xlink:href="agnc-20220331.xsd#agnc_A10YearMaturityMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DerivativeContractTypeDomain_0b6b441e-9498-4851-aa73-a9887f1a917c" xlink:to="loc_agnc_A10YearMaturityMember_8b007cf4-f2ed-40c4-9e84-8a25554ae338" xlink:type="arc" order="8"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FinancialInstrumentAxis_d8c5cc0f-752e-45c2-b178-39c8b0642926" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FinancialInstrumentAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_DerivativeTable_df3bb4b9-04eb-42d9-a0ed-ab4edbc85d68" xlink:to="loc_us-gaap_FinancialInstrumentAxis_d8c5cc0f-752e-45c2-b178-39c8b0642926" xlink:type="arc" order="8"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_d8c5cc0f-752e-45c2-b178-39c8b0642926_default" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_FinancialInstrumentAxis_d8c5cc0f-752e-45c2-b178-39c8b0642926" xlink:to="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_d8c5cc0f-752e-45c2-b178-39c8b0642926_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_a95dd11e-17ee-4c38-aa63-9593652d6c63" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_FinancialInstrumentAxis_d8c5cc0f-752e-45c2-b178-39c8b0642926" xlink:to="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_a95dd11e-17ee-4c38-aa63-9593652d6c63" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FutureMember_c3f1fb14-9f13-4072-b328-00469023186e" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FutureMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_a95dd11e-17ee-4c38-aa63-9593652d6c63" xlink:to="loc_us-gaap_FutureMember_c3f1fb14-9f13-4072-b328-00469023186e" xlink:type="arc" order="0"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.agnc.com/role/DerivativeandOtherHedgingInstrumentsTBASecuritiesbyCouponandIssuerDetails" xlink:type="simple" xlink:href="agnc-20220331.xsd#DerivativeandOtherHedgingInstrumentsTBASecuritiesbyCouponandIssuerDetails"/>
  <link:definitionLink xlink:role="http://www.agnc.com/role/DerivativeandOtherHedgingInstrumentsTBASecuritiesbyCouponandIssuerDetails" xlink:type="extended" id="i51974d531d45492e977d8dbcf1c8683a_DerivativeandOtherHedgingInstrumentsTBASecuritiesbyCouponandIssuerDetails">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DerivativeLineItems_6001075b-69c9-422c-a090-bed6989a268a" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DerivativeLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DerivativeNotionalAmount_17fc7f0c-153e-4979-bb77-8ef477e90a2c" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DerivativeNotionalAmount"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DerivativeLineItems_6001075b-69c9-422c-a090-bed6989a268a" xlink:to="loc_us-gaap_DerivativeNotionalAmount_17fc7f0c-153e-4979-bb77-8ef477e90a2c" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_DerivativeForwardSettlementValue_2e8e3ae2-61fd-4d05-afb8-4e287eaab690" xlink:href="agnc-20220331.xsd#agnc_DerivativeForwardSettlementValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DerivativeLineItems_6001075b-69c9-422c-a090-bed6989a268a" xlink:to="loc_agnc_DerivativeForwardSettlementValue_2e8e3ae2-61fd-4d05-afb8-4e287eaab690" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DerivativeFairValueOfDerivativeAsset_c3e3c781-a04d-4d6b-a90d-66976503f901" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DerivativeFairValueOfDerivativeAsset"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DerivativeLineItems_6001075b-69c9-422c-a090-bed6989a268a" xlink:to="loc_us-gaap_DerivativeFairValueOfDerivativeAsset_c3e3c781-a04d-4d6b-a90d-66976503f901" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DerivativeFairValueOfDerivativeNet_eec5b555-7e53-4b11-95e1-ccab5213a017" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DerivativeFairValueOfDerivativeNet"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DerivativeLineItems_6001075b-69c9-422c-a090-bed6989a268a" xlink:to="loc_us-gaap_DerivativeFairValueOfDerivativeNet_eec5b555-7e53-4b11-95e1-ccab5213a017" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DerivativeTable_757ebcf1-cd2c-4450-b0c1-5645ec5e9b6d" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DerivativeTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_DerivativeLineItems_6001075b-69c9-422c-a090-bed6989a268a" xlink:to="loc_us-gaap_DerivativeTable_757ebcf1-cd2c-4450-b0c1-5645ec5e9b6d" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_DerivativeByMaturityYearsAxis_a2f7b49b-1d79-49c8-bc87-a08f4e31b6d5" xlink:href="agnc-20220331.xsd#agnc_DerivativeByMaturityYearsAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_DerivativeTable_757ebcf1-cd2c-4450-b0c1-5645ec5e9b6d" xlink:to="loc_agnc_DerivativeByMaturityYearsAxis_a2f7b49b-1d79-49c8-bc87-a08f4e31b6d5" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_DerivativeByMaturityYearsDomain_a2f7b49b-1d79-49c8-bc87-a08f4e31b6d5_default" xlink:href="agnc-20220331.xsd#agnc_DerivativeByMaturityYearsDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_agnc_DerivativeByMaturityYearsAxis_a2f7b49b-1d79-49c8-bc87-a08f4e31b6d5" xlink:to="loc_agnc_DerivativeByMaturityYearsDomain_a2f7b49b-1d79-49c8-bc87-a08f4e31b6d5_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_DerivativeByMaturityYearsDomain_94332988-b682-4d80-8b1e-2a324d96f630" xlink:href="agnc-20220331.xsd#agnc_DerivativeByMaturityYearsDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_agnc_DerivativeByMaturityYearsAxis_a2f7b49b-1d79-49c8-bc87-a08f4e31b6d5" xlink:to="loc_agnc_DerivativeByMaturityYearsDomain_94332988-b682-4d80-8b1e-2a324d96f630" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_A30YearMaturityMember_352fd0d8-f2db-44a1-bf63-c6c19a5c3770" xlink:href="agnc-20220331.xsd#agnc_A30YearMaturityMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_agnc_DerivativeByMaturityYearsDomain_94332988-b682-4d80-8b1e-2a324d96f630" xlink:to="loc_agnc_A30YearMaturityMember_352fd0d8-f2db-44a1-bf63-c6c19a5c3770" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_A15YearMaturityMember_a38a99fc-1672-4423-9c60-f2785a9e7014" xlink:href="agnc-20220331.xsd#agnc_A15YearMaturityMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_agnc_DerivativeByMaturityYearsDomain_94332988-b682-4d80-8b1e-2a324d96f630" xlink:to="loc_agnc_A15YearMaturityMember_a38a99fc-1672-4423-9c60-f2785a9e7014" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_DerivativesbyIssuerAxis_9333ec22-2289-4c82-ba61-28495f219eff" xlink:href="agnc-20220331.xsd#agnc_DerivativesbyIssuerAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_DerivativeTable_757ebcf1-cd2c-4450-b0c1-5645ec5e9b6d" xlink:to="loc_agnc_DerivativesbyIssuerAxis_9333ec22-2289-4c82-ba61-28495f219eff" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_DerivativesbyIssuerDomain_9333ec22-2289-4c82-ba61-28495f219eff_default" xlink:href="agnc-20220331.xsd#agnc_DerivativesbyIssuerDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_agnc_DerivativesbyIssuerAxis_9333ec22-2289-4c82-ba61-28495f219eff" xlink:to="loc_agnc_DerivativesbyIssuerDomain_9333ec22-2289-4c82-ba61-28495f219eff_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_DerivativesbyIssuerDomain_00132ef9-590e-47a4-b439-865c9a3130ae" xlink:href="agnc-20220331.xsd#agnc_DerivativesbyIssuerDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_agnc_DerivativesbyIssuerAxis_9333ec22-2289-4c82-ba61-28495f219eff" xlink:to="loc_agnc_DerivativesbyIssuerDomain_00132ef9-590e-47a4-b439-865c9a3130ae" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_GovernmentNationalMortgageAssociationCertificatesAndObligationsGNMAMember_ead684c5-880e-4309-aed0-04c8fa3c318b" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_GovernmentNationalMortgageAssociationCertificatesAndObligationsGNMAMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_agnc_DerivativesbyIssuerDomain_00132ef9-590e-47a4-b439-865c9a3130ae" xlink:to="loc_us-gaap_GovernmentNationalMortgageAssociationCertificatesAndObligationsGNMAMember_ead684c5-880e-4309-aed0-04c8fa3c318b" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FederalHomeLoanMortgageCorporationCertificatesAndObligationsFHLMCMember_38d4a4df-b4ce-458e-a458-829fdcdf7692" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FederalHomeLoanMortgageCorporationCertificatesAndObligationsFHLMCMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_agnc_DerivativesbyIssuerDomain_00132ef9-590e-47a4-b439-865c9a3130ae" xlink:to="loc_us-gaap_FederalHomeLoanMortgageCorporationCertificatesAndObligationsFHLMCMember_38d4a4df-b4ce-458e-a458-829fdcdf7692" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FederalNationalMortgageAssociationCertificatesAndObligationsFNMAMember_ef0950e8-e42b-4856-9dcc-a9299b35ad91" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FederalNationalMortgageAssociationCertificatesAndObligationsFNMAMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_agnc_DerivativesbyIssuerDomain_00132ef9-590e-47a4-b439-865c9a3130ae" xlink:to="loc_us-gaap_FederalNationalMortgageAssociationCertificatesAndObligationsFNMAMember_ef0950e8-e42b-4856-9dcc-a9299b35ad91" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PositionAxis_71b1452a-f3e7-4401-9ca7-d8705c983fbb" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_PositionAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_DerivativeTable_757ebcf1-cd2c-4450-b0c1-5645ec5e9b6d" xlink:to="loc_us-gaap_PositionAxis_71b1452a-f3e7-4401-9ca7-d8705c983fbb" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PositionDomain_71b1452a-f3e7-4401-9ca7-d8705c983fbb_default" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_PositionDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_PositionAxis_71b1452a-f3e7-4401-9ca7-d8705c983fbb" xlink:to="loc_us-gaap_PositionDomain_71b1452a-f3e7-4401-9ca7-d8705c983fbb_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PositionDomain_1effdacd-01eb-47c5-a7f9-ae14c1f3fe81" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_PositionDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_PositionAxis_71b1452a-f3e7-4401-9ca7-d8705c983fbb" xlink:to="loc_us-gaap_PositionDomain_1effdacd-01eb-47c5-a7f9-ae14c1f3fe81" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShortMember_8bfe46bb-fb03-458d-913b-59fd1ea93211" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShortMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PositionDomain_1effdacd-01eb-47c5-a7f9-ae14c1f3fe81" xlink:to="loc_us-gaap_ShortMember_8bfe46bb-fb03-458d-913b-59fd1ea93211" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_DerivativePositionAxis_11315419-6b07-47e5-889a-9a76e78f6c31" xlink:href="agnc-20220331.xsd#agnc_DerivativePositionAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_DerivativeTable_757ebcf1-cd2c-4450-b0c1-5645ec5e9b6d" xlink:to="loc_agnc_DerivativePositionAxis_11315419-6b07-47e5-889a-9a76e78f6c31" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_DerivativePositionDomain_11315419-6b07-47e5-889a-9a76e78f6c31_default" xlink:href="agnc-20220331.xsd#agnc_DerivativePositionDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_agnc_DerivativePositionAxis_11315419-6b07-47e5-889a-9a76e78f6c31" xlink:to="loc_agnc_DerivativePositionDomain_11315419-6b07-47e5-889a-9a76e78f6c31_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_DerivativePositionDomain_8ee0c316-0fe6-4994-a006-e6d7db980601" xlink:href="agnc-20220331.xsd#agnc_DerivativePositionDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_agnc_DerivativePositionAxis_11315419-6b07-47e5-889a-9a76e78f6c31" xlink:to="loc_agnc_DerivativePositionDomain_8ee0c316-0fe6-4994-a006-e6d7db980601" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_A20CouponMember_dfe958bb-156b-46b6-849a-235c42b5e695" xlink:href="agnc-20220331.xsd#agnc_A20CouponMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_agnc_DerivativePositionDomain_8ee0c316-0fe6-4994-a006-e6d7db980601" xlink:to="loc_agnc_A20CouponMember_dfe958bb-156b-46b6-849a-235c42b5e695" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_A2.5CouponMember_157f9229-b5c3-4171-8a4a-850b038c53e4" xlink:href="agnc-20220331.xsd#agnc_A2.5CouponMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_agnc_DerivativePositionDomain_8ee0c316-0fe6-4994-a006-e6d7db980601" xlink:to="loc_agnc_A2.5CouponMember_157f9229-b5c3-4171-8a4a-850b038c53e4" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_A3.0CouponMember_101a6cf3-c838-4f6e-8353-7c5f27bfc88c" xlink:href="agnc-20220331.xsd#agnc_A3.0CouponMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_agnc_DerivativePositionDomain_8ee0c316-0fe6-4994-a006-e6d7db980601" xlink:to="loc_agnc_A3.0CouponMember_101a6cf3-c838-4f6e-8353-7c5f27bfc88c" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_A3.5CouponMember_0999db91-a5ea-4e96-b688-3da0e5b5a008" xlink:href="agnc-20220331.xsd#agnc_A3.5CouponMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_agnc_DerivativePositionDomain_8ee0c316-0fe6-4994-a006-e6d7db980601" xlink:to="loc_agnc_A3.5CouponMember_0999db91-a5ea-4e96-b688-3da0e5b5a008" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_A4.0CouponMember_b811ecd6-97bb-49ac-9192-479cd5cddceb" xlink:href="agnc-20220331.xsd#agnc_A4.0CouponMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_agnc_DerivativePositionDomain_8ee0c316-0fe6-4994-a006-e6d7db980601" xlink:to="loc_agnc_A4.0CouponMember_b811ecd6-97bb-49ac-9192-479cd5cddceb" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_A4.5CouponMember_36563812-2c3d-49ca-8ce6-684edc47bf34" xlink:href="agnc-20220331.xsd#agnc_A4.5CouponMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_agnc_DerivativePositionDomain_8ee0c316-0fe6-4994-a006-e6d7db980601" xlink:to="loc_agnc_A4.5CouponMember_36563812-2c3d-49ca-8ce6-684edc47bf34" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DerivativeInstrumentRiskAxis_2d360623-0836-4344-99dd-35efea709107" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DerivativeInstrumentRiskAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_DerivativeTable_757ebcf1-cd2c-4450-b0c1-5645ec5e9b6d" xlink:to="loc_us-gaap_DerivativeInstrumentRiskAxis_2d360623-0836-4344-99dd-35efea709107" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DerivativeContractTypeDomain_2d360623-0836-4344-99dd-35efea709107_default" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DerivativeContractTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_DerivativeInstrumentRiskAxis_2d360623-0836-4344-99dd-35efea709107" xlink:to="loc_us-gaap_DerivativeContractTypeDomain_2d360623-0836-4344-99dd-35efea709107_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DerivativeContractTypeDomain_06bd0759-ad04-4687-8042-b0c8f40dd400" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DerivativeContractTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_DerivativeInstrumentRiskAxis_2d360623-0836-4344-99dd-35efea709107" xlink:to="loc_us-gaap_DerivativeContractTypeDomain_06bd0759-ad04-4687-8042-b0c8f40dd400" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_TBAAndForwardSettlingSecuritiesMember_22057a78-f8cb-48c8-a0d8-8badf93970c4" xlink:href="agnc-20220331.xsd#agnc_TBAAndForwardSettlingSecuritiesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DerivativeContractTypeDomain_06bd0759-ad04-4687-8042-b0c8f40dd400" xlink:to="loc_agnc_TBAAndForwardSettlingSecuritiesMember_22057a78-f8cb-48c8-a0d8-8badf93970c4" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_A15YearMaturityMember_9ecada7e-f9c3-4944-9b5e-cbeb894e4c97" xlink:href="agnc-20220331.xsd#agnc_A15YearMaturityMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DerivativeContractTypeDomain_06bd0759-ad04-4687-8042-b0c8f40dd400" xlink:to="loc_agnc_A15YearMaturityMember_9ecada7e-f9c3-4944-9b5e-cbeb894e4c97" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_A30YearMaturityMember_a81495d6-8616-41c6-ad64-3321792f51a4" xlink:href="agnc-20220331.xsd#agnc_A30YearMaturityMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DerivativeContractTypeDomain_06bd0759-ad04-4687-8042-b0c8f40dd400" xlink:to="loc_agnc_A30YearMaturityMember_a81495d6-8616-41c6-ad64-3321792f51a4" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FederalNationalMortgageAssociationCertificatesAndObligationsFNMAMember_7c948057-3dce-4dc1-b59c-9bbf20a6cc9d" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FederalNationalMortgageAssociationCertificatesAndObligationsFNMAMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DerivativeContractTypeDomain_06bd0759-ad04-4687-8042-b0c8f40dd400" xlink:to="loc_us-gaap_FederalNationalMortgageAssociationCertificatesAndObligationsFNMAMember_7c948057-3dce-4dc1-b59c-9bbf20a6cc9d" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FederalHomeLoanMortgageCorporationCertificatesAndObligationsFHLMCMember_dab14661-1c0b-44e7-8cda-cd6c53ca3100" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FederalHomeLoanMortgageCorporationCertificatesAndObligationsFHLMCMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DerivativeContractTypeDomain_06bd0759-ad04-4687-8042-b0c8f40dd400" xlink:to="loc_us-gaap_FederalHomeLoanMortgageCorporationCertificatesAndObligationsFHLMCMember_dab14661-1c0b-44e7-8cda-cd6c53ca3100" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_GovernmentNationalMortgageAssociationCertificatesAndObligationsGNMAMember_23adf8b4-353c-4ab4-8bcc-dfde4c5b043b" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_GovernmentNationalMortgageAssociationCertificatesAndObligationsGNMAMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DerivativeContractTypeDomain_06bd0759-ad04-4687-8042-b0c8f40dd400" xlink:to="loc_us-gaap_GovernmentNationalMortgageAssociationCertificatesAndObligationsGNMAMember_23adf8b4-353c-4ab4-8bcc-dfde4c5b043b" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_ForwardSettlingNonAgencySecuritiesMember_bb3d5f18-2407-4784-b427-baf2d49a4f9f" xlink:href="agnc-20220331.xsd#agnc_ForwardSettlingNonAgencySecuritiesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DerivativeContractTypeDomain_06bd0759-ad04-4687-8042-b0c8f40dd400" xlink:to="loc_agnc_ForwardSettlingNonAgencySecuritiesMember_bb3d5f18-2407-4784-b427-baf2d49a4f9f" xlink:type="arc" order="6"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.agnc.com/role/DerivativeandOtherHedgingInstrumentsEffectOfDerivativeInstrumentsNotDesignatedAsHedgesOnComprehensiveIncomeStatementDetails" xlink:type="simple" xlink:href="agnc-20220331.xsd#DerivativeandOtherHedgingInstrumentsEffectOfDerivativeInstrumentsNotDesignatedAsHedgesOnComprehensiveIncomeStatementDetails"/>
  <link:definitionLink xlink:role="http://www.agnc.com/role/DerivativeandOtherHedgingInstrumentsEffectOfDerivativeInstrumentsNotDesignatedAsHedgesOnComprehensiveIncomeStatementDetails" xlink:type="extended" id="i74680f08849544508df2c5ecb3ac2a30_DerivativeandOtherHedgingInstrumentsEffectOfDerivativeInstrumentsNotDesignatedAsHedgesOnComprehensiveIncomeStatementDetails">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StatementLineItems_ae995cba-4935-4d55-b915-282976aace9e" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_StatementLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_ChangesinDerivativeandOtherHedgePortfolioRollForward_431fc144-c244-4daf-9661-e1a3d679dc75" xlink:href="agnc-20220331.xsd#agnc_ChangesinDerivativeandOtherHedgePortfolioRollForward"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_ae995cba-4935-4d55-b915-282976aace9e" xlink:to="loc_agnc_ChangesinDerivativeandOtherHedgePortfolioRollForward_431fc144-c244-4daf-9661-e1a3d679dc75" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DerivativeNotionalAmount_0bed339b-238a-41b4-9545-0a2650840322" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DerivativeNotionalAmount"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_agnc_ChangesinDerivativeandOtherHedgePortfolioRollForward_431fc144-c244-4daf-9661-e1a3d679dc75" xlink:to="loc_us-gaap_DerivativeNotionalAmount_0bed339b-238a-41b4-9545-0a2650840322" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_NotionalAmountOfDerivativesNotDesignatedAsHedgingInstrumentsAdditionsDuringPeriod_0b60f334-49e4-4736-a587-9670541d807a" xlink:href="agnc-20220331.xsd#agnc_NotionalAmountOfDerivativesNotDesignatedAsHedgingInstrumentsAdditionsDuringPeriod"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_agnc_ChangesinDerivativeandOtherHedgePortfolioRollForward_431fc144-c244-4daf-9661-e1a3d679dc75" xlink:to="loc_agnc_NotionalAmountOfDerivativesNotDesignatedAsHedgingInstrumentsAdditionsDuringPeriod_0b60f334-49e4-4736-a587-9670541d807a" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_NotionalAmountOfDerivativesNotDesignatedAsHedgingInstrumentsSettlementExpirationDuringPeriod_e788d501-c5fc-466f-b07b-24b7151689d5" xlink:href="agnc-20220331.xsd#agnc_NotionalAmountOfDerivativesNotDesignatedAsHedgingInstrumentsSettlementExpirationDuringPeriod"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_agnc_ChangesinDerivativeandOtherHedgePortfolioRollForward_431fc144-c244-4daf-9661-e1a3d679dc75" xlink:to="loc_agnc_NotionalAmountOfDerivativesNotDesignatedAsHedgingInstrumentsSettlementExpirationDuringPeriod_e788d501-c5fc-466f-b07b-24b7151689d5" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DerivativeLiabilityNotionalAmount_ce5d6a7a-6aa5-4e1b-a985-712ef4729843" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DerivativeLiabilityNotionalAmount"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_agnc_ChangesinDerivativeandOtherHedgePortfolioRollForward_431fc144-c244-4daf-9661-e1a3d679dc75" xlink:to="loc_us-gaap_DerivativeLiabilityNotionalAmount_ce5d6a7a-6aa5-4e1b-a985-712ef4729843" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DerivativeInstrumentsNotDesignatedAsHedgingInstrumentsGainLossNet_dfee8834-f33f-4e17-a7d7-31d02f547210" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DerivativeInstrumentsNotDesignatedAsHedgingInstrumentsGainLossNet"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_ae995cba-4935-4d55-b915-282976aace9e" xlink:to="loc_us-gaap_DerivativeInstrumentsNotDesignatedAsHedgingInstrumentsGainLossNet_dfee8834-f33f-4e17-a7d7-31d02f547210" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_TradingSecurities_afe841d2-2dda-47e3-b178-73101c049e9c" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_TradingSecurities"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_ae995cba-4935-4d55-b915-282976aace9e" xlink:to="loc_us-gaap_TradingSecurities_afe841d2-2dda-47e3-b178-73101c049e9c" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_TradingSecuritiesAddedDuringthePeriod_45cacbad-9e4e-436d-8684-e23046616bcf" xlink:href="agnc-20220331.xsd#agnc_TradingSecuritiesAddedDuringthePeriod"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_ae995cba-4935-4d55-b915-282976aace9e" xlink:to="loc_agnc_TradingSecuritiesAddedDuringthePeriod_45cacbad-9e4e-436d-8684-e23046616bcf" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_NotionalAmountOfTradingSecuritiesSettlementExpirationDuringThePeriod_e1895a04-b476-447c-b158-f78e4a4074de" xlink:href="agnc-20220331.xsd#agnc_NotionalAmountOfTradingSecuritiesSettlementExpirationDuringThePeriod"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_ae995cba-4935-4d55-b915-282976aace9e" xlink:to="loc_agnc_NotionalAmountOfTradingSecuritiesSettlementExpirationDuringThePeriod_e1895a04-b476-447c-b158-f78e4a4074de" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_GainLossOnOtherDebt_178c90e3-f58c-40d0-9af2-2f7925b14db6" xlink:href="agnc-20220331.xsd#agnc_GainLossOnOtherDebt"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_ae995cba-4935-4d55-b915-282976aace9e" xlink:to="loc_agnc_GainLossOnOtherDebt_178c90e3-f58c-40d0-9af2-2f7925b14db6" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_GainsLossesOnExtinguishmentOfDebt_fbe1e7f6-164a-4be9-ab08-11570d03ee34" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_GainsLossesOnExtinguishmentOfDebt"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_ae995cba-4935-4d55-b915-282976aace9e" xlink:to="loc_us-gaap_GainsLossesOnExtinguishmentOfDebt_fbe1e7f6-164a-4be9-ab08-11570d03ee34" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DerivativeTable_fa31dff3-ec35-428e-a954-53e61376c7b9" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DerivativeTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_StatementLineItems_ae995cba-4935-4d55-b915-282976aace9e" xlink:to="loc_us-gaap_DerivativeTable_fa31dff3-ec35-428e-a954-53e61376c7b9" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FinancialInstrumentAxis_b82b2998-3eda-4321-aec4-95e37217b127" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FinancialInstrumentAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_DerivativeTable_fa31dff3-ec35-428e-a954-53e61376c7b9" xlink:to="loc_us-gaap_FinancialInstrumentAxis_b82b2998-3eda-4321-aec4-95e37217b127" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_b82b2998-3eda-4321-aec4-95e37217b127_default" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_FinancialInstrumentAxis_b82b2998-3eda-4321-aec4-95e37217b127" xlink:to="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_b82b2998-3eda-4321-aec4-95e37217b127_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_6135496b-4953-4354-90a6-f0fa939fedb1" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_FinancialInstrumentAxis_b82b2998-3eda-4321-aec4-95e37217b127" xlink:to="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_6135496b-4953-4354-90a6-f0fa939fedb1" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FutureMember_b1bd232e-2757-4927-baa8-b6d17b8ed8f1" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FutureMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_6135496b-4953-4354-90a6-f0fa939fedb1" xlink:to="loc_us-gaap_FutureMember_b1bd232e-2757-4927-baa8-b6d17b8ed8f1" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PositionAxis_7db37f01-6b3f-4893-823e-442e2f016528" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_PositionAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_DerivativeTable_fa31dff3-ec35-428e-a954-53e61376c7b9" xlink:to="loc_us-gaap_PositionAxis_7db37f01-6b3f-4893-823e-442e2f016528" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PositionDomain_7db37f01-6b3f-4893-823e-442e2f016528_default" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_PositionDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_PositionAxis_7db37f01-6b3f-4893-823e-442e2f016528" xlink:to="loc_us-gaap_PositionDomain_7db37f01-6b3f-4893-823e-442e2f016528_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PositionDomain_206bf8db-c0b8-48a6-80ed-c70ddc9bf60b" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_PositionDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_PositionAxis_7db37f01-6b3f-4893-823e-442e2f016528" xlink:to="loc_us-gaap_PositionDomain_206bf8db-c0b8-48a6-80ed-c70ddc9bf60b" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShortMember_b7a3b12c-0f4e-4e15-a6e3-6fa55b23be47" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShortMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PositionDomain_206bf8db-c0b8-48a6-80ed-c70ddc9bf60b" xlink:to="loc_us-gaap_ShortMember_b7a3b12c-0f4e-4e15-a6e3-6fa55b23be47" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LongMember_2ce6c89a-9674-4af9-a7cc-7160de278c50" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_LongMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PositionDomain_206bf8db-c0b8-48a6-80ed-c70ddc9bf60b" xlink:to="loc_us-gaap_LongMember_2ce6c89a-9674-4af9-a7cc-7160de278c50" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_HedgingDesignationAxis_1e6fb853-adcb-465b-b301-35d7c912fb71" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_HedgingDesignationAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_DerivativeTable_fa31dff3-ec35-428e-a954-53e61376c7b9" xlink:to="loc_us-gaap_HedgingDesignationAxis_1e6fb853-adcb-465b-b301-35d7c912fb71" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_HedgingDesignationDomain_1e6fb853-adcb-465b-b301-35d7c912fb71_default" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_HedgingDesignationDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_HedgingDesignationAxis_1e6fb853-adcb-465b-b301-35d7c912fb71" xlink:to="loc_us-gaap_HedgingDesignationDomain_1e6fb853-adcb-465b-b301-35d7c912fb71_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_HedgingDesignationDomain_8d378a1a-5894-4ed3-bbf4-a293e9850802" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_HedgingDesignationDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_HedgingDesignationAxis_1e6fb853-adcb-465b-b301-35d7c912fb71" xlink:to="loc_us-gaap_HedgingDesignationDomain_8d378a1a-5894-4ed3-bbf4-a293e9850802" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_NondesignatedMember_cb4dde32-1f74-4191-8e02-47ec5783ccd9" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_NondesignatedMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_HedgingDesignationDomain_8d378a1a-5894-4ed3-bbf4-a293e9850802" xlink:to="loc_us-gaap_NondesignatedMember_cb4dde32-1f74-4191-8e02-47ec5783ccd9" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_InvestmentTypeAxis_aff9e174-8fbd-4fc1-b485-b9340dcb946e" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_InvestmentTypeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_DerivativeTable_fa31dff3-ec35-428e-a954-53e61376c7b9" xlink:to="loc_us-gaap_InvestmentTypeAxis_aff9e174-8fbd-4fc1-b485-b9340dcb946e" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_InvestmentTypeCategorizationMember_aff9e174-8fbd-4fc1-b485-b9340dcb946e_default" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_InvestmentTypeCategorizationMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_InvestmentTypeAxis_aff9e174-8fbd-4fc1-b485-b9340dcb946e" xlink:to="loc_us-gaap_InvestmentTypeCategorizationMember_aff9e174-8fbd-4fc1-b485-b9340dcb946e_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_InvestmentTypeCategorizationMember_806b63da-1a33-44a4-b789-3c008fc15a8b" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_InvestmentTypeCategorizationMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_InvestmentTypeAxis_aff9e174-8fbd-4fc1-b485-b9340dcb946e" xlink:to="loc_us-gaap_InvestmentTypeCategorizationMember_806b63da-1a33-44a4-b789-3c008fc15a8b" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_OtherDerivativesMember_ef1a39c5-6a90-4881-ad42-efdaf9cd903e" xlink:href="agnc-20220331.xsd#agnc_OtherDerivativesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_InvestmentTypeCategorizationMember_806b63da-1a33-44a4-b789-3c008fc15a8b" xlink:to="loc_agnc_OtherDerivativesMember_ef1a39c5-6a90-4881-ad42-efdaf9cd903e" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_InterestOnlyAndPrincipalOnlyStripMember_f4f42075-e641-4b2d-a4ef-18af2cbb2b67" xlink:href="agnc-20220331.xsd#agnc_InterestOnlyAndPrincipalOnlyStripMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_InvestmentTypeCategorizationMember_806b63da-1a33-44a4-b789-3c008fc15a8b" xlink:to="loc_agnc_InterestOnlyAndPrincipalOnlyStripMember_f4f42075-e641-4b2d-a4ef-18af2cbb2b67" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DerivativeInstrumentRiskAxis_8bfb6c41-798a-4981-b0ab-b114e126bb26" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DerivativeInstrumentRiskAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_DerivativeTable_fa31dff3-ec35-428e-a954-53e61376c7b9" xlink:to="loc_us-gaap_DerivativeInstrumentRiskAxis_8bfb6c41-798a-4981-b0ab-b114e126bb26" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DerivativeContractTypeDomain_8bfb6c41-798a-4981-b0ab-b114e126bb26_default" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DerivativeContractTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_DerivativeInstrumentRiskAxis_8bfb6c41-798a-4981-b0ab-b114e126bb26" xlink:to="loc_us-gaap_DerivativeContractTypeDomain_8bfb6c41-798a-4981-b0ab-b114e126bb26_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DerivativeContractTypeDomain_ab8f81f3-f035-4fa0-8157-a12226a13479" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DerivativeContractTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_DerivativeInstrumentRiskAxis_8bfb6c41-798a-4981-b0ab-b114e126bb26" xlink:to="loc_us-gaap_DerivativeContractTypeDomain_ab8f81f3-f035-4fa0-8157-a12226a13479" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_InterestrateswapreceiverMember_4c5587b8-76ce-4ae1-ae76-cf6037080d86" xlink:href="agnc-20220331.xsd#agnc_InterestrateswapreceiverMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DerivativeContractTypeDomain_ab8f81f3-f035-4fa0-8157-a12226a13479" xlink:to="loc_agnc_InterestrateswapreceiverMember_4c5587b8-76ce-4ae1-ae76-cf6037080d86" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_PayerSwaptionMember_292171d0-9e39-48a8-8895-5749c9276513" xlink:href="agnc-20220331.xsd#agnc_PayerSwaptionMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DerivativeContractTypeDomain_ab8f81f3-f035-4fa0-8157-a12226a13479" xlink:to="loc_agnc_PayerSwaptionMember_292171d0-9e39-48a8-8895-5749c9276513" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FutureMember_d4f8fa17-e779-4c7e-a8c9-3ce1d30a9bd4" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FutureMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DerivativeContractTypeDomain_ab8f81f3-f035-4fa0-8157-a12226a13479" xlink:to="loc_us-gaap_FutureMember_d4f8fa17-e779-4c7e-a8c9-3ce1d30a9bd4" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_InterestRateSwaptionMember_f522c5a8-8c8a-4baf-af1f-15a3bb5e5b81" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_InterestRateSwaptionMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DerivativeContractTypeDomain_ab8f81f3-f035-4fa0-8157-a12226a13479" xlink:to="loc_us-gaap_InterestRateSwaptionMember_f522c5a8-8c8a-4baf-af1f-15a3bb5e5b81" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_TBAAndForwardSettlingSecuritiesMember_fdc7b1fa-f465-40be-900c-39e9fbf71d75" xlink:href="agnc-20220331.xsd#agnc_TBAAndForwardSettlingSecuritiesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DerivativeContractTypeDomain_ab8f81f3-f035-4fa0-8157-a12226a13479" xlink:to="loc_agnc_TBAAndForwardSettlingSecuritiesMember_fdc7b1fa-f465-40be-900c-39e9fbf71d75" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_PurchasesOfTBAsAndForwardSettlingSecuritiesMember_08487cea-54ff-42a6-b231-dcc2df385682" xlink:href="agnc-20220331.xsd#agnc_PurchasesOfTBAsAndForwardSettlingSecuritiesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DerivativeContractTypeDomain_ab8f81f3-f035-4fa0-8157-a12226a13479" xlink:to="loc_agnc_PurchasesOfTBAsAndForwardSettlingSecuritiesMember_08487cea-54ff-42a6-b231-dcc2df385682" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_InterestRateSwapMember_4576ac56-9266-4038-8793-9e23a69cd8b7" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_InterestRateSwapMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DerivativeContractTypeDomain_ab8f81f3-f035-4fa0-8157-a12226a13479" xlink:to="loc_us-gaap_InterestRateSwapMember_4576ac56-9266-4038-8793-9e23a69cd8b7" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_USTreasurySecuritiesMember_9f84843b-949f-49c3-915b-21f1d577e850" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_USTreasurySecuritiesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DerivativeContractTypeDomain_ab8f81f3-f035-4fa0-8157-a12226a13479" xlink:to="loc_us-gaap_USTreasurySecuritiesMember_9f84843b-949f-49c3-915b-21f1d577e850" xlink:type="arc" order="7"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_ReceiverSwaptionMember_940549fe-9fab-41e2-a954-92526cd9a26c" xlink:href="agnc-20220331.xsd#agnc_ReceiverSwaptionMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DerivativeContractTypeDomain_ab8f81f3-f035-4fa0-8157-a12226a13479" xlink:to="loc_agnc_ReceiverSwaptionMember_940549fe-9fab-41e2-a954-92526cd9a26c" xlink:type="arc" order="8"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_ForwardSettlingNonAgencySecuritiesMember_438b577c-c207-4dcd-b996-e4b2a4d76650" xlink:href="agnc-20220331.xsd#agnc_ForwardSettlingNonAgencySecuritiesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DerivativeContractTypeDomain_ab8f81f3-f035-4fa0-8157-a12226a13479" xlink:to="loc_agnc_ForwardSettlingNonAgencySecuritiesMember_438b577c-c207-4dcd-b996-e4b2a4d76650" xlink:type="arc" order="9"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_PurchasesOfForwardSettlingNonAgencySecuritiesMember_a073b222-6b9f-4bca-a8a6-f62cb34d6ad8" xlink:href="agnc-20220331.xsd#agnc_PurchasesOfForwardSettlingNonAgencySecuritiesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DerivativeContractTypeDomain_ab8f81f3-f035-4fa0-8157-a12226a13479" xlink:to="loc_agnc_PurchasesOfForwardSettlingNonAgencySecuritiesMember_a073b222-6b9f-4bca-a8a6-f62cb34d6ad8" xlink:type="arc" order="10"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CreditDefaultSwapMember_75f7b904-a53f-4ea9-ada7-03aba131699e" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_CreditDefaultSwapMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DerivativeContractTypeDomain_ab8f81f3-f035-4fa0-8157-a12226a13479" xlink:to="loc_us-gaap_CreditDefaultSwapMember_75f7b904-a53f-4ea9-ada7-03aba131699e" xlink:type="arc" order="11"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CreditDefaultSwapBuyingProtectionMember_556643e0-3793-48a8-921b-1fafa88c2f26" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_CreditDefaultSwapBuyingProtectionMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DerivativeContractTypeDomain_ab8f81f3-f035-4fa0-8157-a12226a13479" xlink:to="loc_us-gaap_CreditDefaultSwapBuyingProtectionMember_556643e0-3793-48a8-921b-1fafa88c2f26" xlink:type="arc" order="12"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncomeStatementLocationAxis_fd5a1e6a-8ece-4d05-9b24-520fb64d5073" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_IncomeStatementLocationAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_DerivativeTable_fa31dff3-ec35-428e-a954-53e61376c7b9" xlink:to="loc_us-gaap_IncomeStatementLocationAxis_fd5a1e6a-8ece-4d05-9b24-520fb64d5073" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncomeStatementLocationDomain_fd5a1e6a-8ece-4d05-9b24-520fb64d5073_default" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_IncomeStatementLocationDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_IncomeStatementLocationAxis_fd5a1e6a-8ece-4d05-9b24-520fb64d5073" xlink:to="loc_us-gaap_IncomeStatementLocationDomain_fd5a1e6a-8ece-4d05-9b24-520fb64d5073_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncomeStatementLocationDomain_2422b921-00d8-4017-abca-17a906934406" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_IncomeStatementLocationDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_IncomeStatementLocationAxis_fd5a1e6a-8ece-4d05-9b24-520fb64d5073" xlink:to="loc_us-gaap_IncomeStatementLocationDomain_2422b921-00d8-4017-abca-17a906934406" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_InterestOnlyAndPrincipalOnlyStripMember_88143247-2ad1-47fb-8674-d43ea21130b9" xlink:href="agnc-20220331.xsd#agnc_InterestOnlyAndPrincipalOnlyStripMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncomeStatementLocationDomain_2422b921-00d8-4017-abca-17a906934406" xlink:to="loc_agnc_InterestOnlyAndPrincipalOnlyStripMember_88143247-2ad1-47fb-8674-d43ea21130b9" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_InterestRateSwapMember_506a63f1-4386-4888-903d-b2fe028ed090" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_InterestRateSwapMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncomeStatementLocationDomain_2422b921-00d8-4017-abca-17a906934406" xlink:to="loc_us-gaap_InterestRateSwapMember_506a63f1-4386-4888-903d-b2fe028ed090" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_PurchasesOfTBAsAndForwardSettlingSecuritiesMember_30d4a607-21a0-4973-9a94-411bf1d3dfcb" xlink:href="agnc-20220331.xsd#agnc_PurchasesOfTBAsAndForwardSettlingSecuritiesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncomeStatementLocationDomain_2422b921-00d8-4017-abca-17a906934406" xlink:to="loc_agnc_PurchasesOfTBAsAndForwardSettlingSecuritiesMember_30d4a607-21a0-4973-9a94-411bf1d3dfcb" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_USTreasurySecuritiesMember_08afac59-5c51-4b11-bb7e-b9f3534c52c5" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_USTreasurySecuritiesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncomeStatementLocationDomain_2422b921-00d8-4017-abca-17a906934406" xlink:to="loc_us-gaap_USTreasurySecuritiesMember_08afac59-5c51-4b11-bb7e-b9f3534c52c5" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OptionIndexedToIssuersEquityTypeAxis_c4622941-a403-4ddb-873e-f8e30f8deeda" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_OptionIndexedToIssuersEquityTypeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_DerivativeTable_fa31dff3-ec35-428e-a954-53e61376c7b9" xlink:to="loc_us-gaap_OptionIndexedToIssuersEquityTypeAxis_c4622941-a403-4ddb-873e-f8e30f8deeda" xlink:type="arc" order="7"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OptionIndexedToIssuersEquityTypeDomain_c4622941-a403-4ddb-873e-f8e30f8deeda_default" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_OptionIndexedToIssuersEquityTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_OptionIndexedToIssuersEquityTypeAxis_c4622941-a403-4ddb-873e-f8e30f8deeda" xlink:to="loc_us-gaap_OptionIndexedToIssuersEquityTypeDomain_c4622941-a403-4ddb-873e-f8e30f8deeda_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OptionIndexedToIssuersEquityTypeDomain_7a25f327-ae6a-4df2-be8e-4c3010dfc83d" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_OptionIndexedToIssuersEquityTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_OptionIndexedToIssuersEquityTypeAxis_c4622941-a403-4ddb-873e-f8e30f8deeda" xlink:to="loc_us-gaap_OptionIndexedToIssuersEquityTypeDomain_7a25f327-ae6a-4df2-be8e-4c3010dfc83d" xlink:type="arc" order="1"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.agnc.com/role/PledgedAssetsRepurchaseAgreementswithCounterpartiesGreaterthanorEqualto5ofEquityatRiskDetails" xlink:type="simple" xlink:href="agnc-20220331.xsd#PledgedAssetsRepurchaseAgreementswithCounterpartiesGreaterthanorEqualto5ofEquityatRiskDetails"/>
  <link:definitionLink xlink:role="http://www.agnc.com/role/PledgedAssetsRepurchaseAgreementswithCounterpartiesGreaterthanorEqualto5ofEquityatRiskDetails" xlink:type="extended" id="i77525773441944c4a3c95e6f05213112_PledgedAssetsRepurchaseAgreementswithCounterpartiesGreaterthanorEqualto5ofEquityatRiskDetails">
    <link:loc xlink:type="locator" xlink:label="loc_agnc_RepurchaseAgreementswithCounterpartiesGreaterthanorequalto5ofEquityatRiskLineItems_85e3c8fb-a80a-47b2-b029-4b56ed618836" xlink:href="agnc-20220331.xsd#agnc_RepurchaseAgreementswithCounterpartiesGreaterthanorequalto5ofEquityatRiskLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SecuritiesSoldUnderAgreementsToRepurchase_73dd35e1-c229-4761-9852-9b16dd6edea8" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_SecuritiesSoldUnderAgreementsToRepurchase"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_agnc_RepurchaseAgreementswithCounterpartiesGreaterthanorequalto5ofEquityatRiskLineItems_85e3c8fb-a80a-47b2-b029-4b56ed618836" xlink:to="loc_us-gaap_SecuritiesSoldUnderAgreementsToRepurchase_73dd35e1-c229-4761-9852-9b16dd6edea8" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_RiskOfRepurchaseAgreementToStockholdersEquity_4b21017b-f3d2-4a5e-94ba-87ca731b58d1" xlink:href="agnc-20220331.xsd#agnc_RiskOfRepurchaseAgreementToStockholdersEquity"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_agnc_RepurchaseAgreementswithCounterpartiesGreaterthanorequalto5ofEquityatRiskLineItems_85e3c8fb-a80a-47b2-b029-4b56ed618836" xlink:to="loc_agnc_RiskOfRepurchaseAgreementToStockholdersEquity_4b21017b-f3d2-4a5e-94ba-87ca731b58d1" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_RepurchaseAgreementsWeightedAverageDaysToMaturity_806c95ae-2b37-4966-b137-1a8d39d1c00e" xlink:href="agnc-20220331.xsd#agnc_RepurchaseAgreementsWeightedAverageDaysToMaturity"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_agnc_RepurchaseAgreementswithCounterpartiesGreaterthanorequalto5ofEquityatRiskLineItems_85e3c8fb-a80a-47b2-b029-4b56ed618836" xlink:to="loc_agnc_RepurchaseAgreementsWeightedAverageDaysToMaturity_806c95ae-2b37-4966-b137-1a8d39d1c00e" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_CounterpartyExposureNet_ff727ab8-6912-4226-a881-27e4a0d0cf11" xlink:href="agnc-20220331.xsd#agnc_CounterpartyExposureNet"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_agnc_RepurchaseAgreementswithCounterpartiesGreaterthanorequalto5ofEquityatRiskLineItems_85e3c8fb-a80a-47b2-b029-4b56ed618836" xlink:to="loc_agnc_CounterpartyExposureNet_ff727ab8-6912-4226-a881-27e4a0d0cf11" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_RepurchaseAgreementsWeightedAverageMonthsToMaturity_4a9a5a50-80ae-445c-b68b-cb3fec97de65" xlink:href="agnc-20220331.xsd#agnc_RepurchaseAgreementsWeightedAverageMonthsToMaturity"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_agnc_RepurchaseAgreementswithCounterpartiesGreaterthanorequalto5ofEquityatRiskLineItems_85e3c8fb-a80a-47b2-b029-4b56ed618836" xlink:to="loc_agnc_RepurchaseAgreementsWeightedAverageMonthsToMaturity_4a9a5a50-80ae-445c-b68b-cb3fec97de65" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_RepurchaseAgreementswithCounterpartiesGreaterthanorequalto5ofEquityatRiskTable_1e46f5a8-39cc-4f10-88a0-6045b9429fd0" xlink:href="agnc-20220331.xsd#agnc_RepurchaseAgreementswithCounterpartiesGreaterthanorequalto5ofEquityatRiskTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_agnc_RepurchaseAgreementswithCounterpartiesGreaterthanorequalto5ofEquityatRiskLineItems_85e3c8fb-a80a-47b2-b029-4b56ed618836" xlink:to="loc_agnc_RepurchaseAgreementswithCounterpartiesGreaterthanorequalto5ofEquityatRiskTable_1e46f5a8-39cc-4f10-88a0-6045b9429fd0" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_CounterpartyNameAxis_0dd5c954-52a9-4c82-a96e-19c45ab0110a" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_CounterpartyNameAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_agnc_RepurchaseAgreementswithCounterpartiesGreaterthanorequalto5ofEquityatRiskTable_1e46f5a8-39cc-4f10-88a0-6045b9429fd0" xlink:to="loc_srt_CounterpartyNameAxis_0dd5c954-52a9-4c82-a96e-19c45ab0110a" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RepurchaseAgreementCounterpartyNameDomain_0dd5c954-52a9-4c82-a96e-19c45ab0110a_default" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_RepurchaseAgreementCounterpartyNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_CounterpartyNameAxis_0dd5c954-52a9-4c82-a96e-19c45ab0110a" xlink:to="loc_srt_RepurchaseAgreementCounterpartyNameDomain_0dd5c954-52a9-4c82-a96e-19c45ab0110a_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RepurchaseAgreementCounterpartyNameDomain_42f1b8bf-643e-4574-a38c-6477861b9f2c" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_RepurchaseAgreementCounterpartyNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_CounterpartyNameAxis_0dd5c954-52a9-4c82-a96e-19c45ab0110a" xlink:to="loc_srt_RepurchaseAgreementCounterpartyNameDomain_42f1b8bf-643e-4574-a38c-6477861b9f2c" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_FICCMember_99000083-052f-40ee-8ee9-888686f2e1bd" xlink:href="agnc-20220331.xsd#agnc_FICCMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RepurchaseAgreementCounterpartyNameDomain_42f1b8bf-643e-4574-a38c-6477861b9f2c" xlink:to="loc_agnc_FICCMember_99000083-052f-40ee-8ee9-888686f2e1bd" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_J.P.MorganSecuritiesLLCMember_37773a1e-8b1b-47c0-81f4-2d67e247b61d" xlink:href="agnc-20220331.xsd#agnc_J.P.MorganSecuritiesLLCMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RepurchaseAgreementCounterpartyNameDomain_42f1b8bf-643e-4574-a38c-6477861b9f2c" xlink:to="loc_agnc_J.P.MorganSecuritiesLLCMember_37773a1e-8b1b-47c0-81f4-2d67e247b61d" xlink:type="arc" order="1"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.agnc.com/role/PledgedAssetsAssetsPledgedasCollateralDetails" xlink:type="simple" xlink:href="agnc-20220331.xsd#PledgedAssetsAssetsPledgedasCollateralDetails"/>
  <link:definitionLink xlink:role="http://www.agnc.com/role/PledgedAssetsAssetsPledgedasCollateralDetails" xlink:type="extended" id="i4a7dcb381c1944c29228e13f8a0d2b4d_PledgedAssetsAssetsPledgedasCollateralDetails">
    <link:loc xlink:type="locator" xlink:label="loc_agnc_OffsettingAssetsAndLiabilitiesLineItems_c6e3d711-5e52-446d-803e-0575ccb4b554" xlink:href="agnc-20220331.xsd#agnc_OffsettingAssetsAndLiabilitiesLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_RetainedInterestsinConsolidatedVIEsPledgedasCollateralUnderRepurchaseAgreements_3bb40171-d3f2-4ae7-88ca-d116b79139e7" xlink:href="agnc-20220331.xsd#agnc_RetainedInterestsinConsolidatedVIEsPledgedasCollateralUnderRepurchaseAgreements"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_agnc_OffsettingAssetsAndLiabilitiesLineItems_c6e3d711-5e52-446d-803e-0575ccb4b554" xlink:to="loc_agnc_RetainedInterestsinConsolidatedVIEsPledgedasCollateralUnderRepurchaseAgreements_3bb40171-d3f2-4ae7-88ca-d116b79139e7" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FederalHomeLoanBankStock_fe05667f-0a8c-49b1-ba84-e41d34d946ff" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FederalHomeLoanBankStock"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_agnc_OffsettingAssetsAndLiabilitiesLineItems_c6e3d711-5e52-446d-803e-0575ccb4b554" xlink:to="loc_us-gaap_FederalHomeLoanBankStock_fe05667f-0a8c-49b1-ba84-e41d34d946ff" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_AvailableForSaleSecuritiesPledgedAsCollateralAccruedInterest_d231e5f3-3ee3-49e8-930b-ba9f14297125" xlink:href="agnc-20220331.xsd#agnc_AvailableForSaleSecuritiesPledgedAsCollateralAccruedInterest"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_agnc_OffsettingAssetsAndLiabilitiesLineItems_c6e3d711-5e52-446d-803e-0575ccb4b554" xlink:to="loc_agnc_AvailableForSaleSecuritiesPledgedAsCollateralAccruedInterest_d231e5f3-3ee3-49e8-930b-ba9f14297125" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RestrictedCashAndCashEquivalents_80d70890-b0a2-444f-993f-375afbee2239" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_RestrictedCashAndCashEquivalents"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_agnc_OffsettingAssetsAndLiabilitiesLineItems_c6e3d711-5e52-446d-803e-0575ccb4b554" xlink:to="loc_us-gaap_RestrictedCashAndCashEquivalents_80d70890-b0a2-444f-993f-375afbee2239" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_TotalFairValueofSecuritiesPledgedandAccruedInterest_58c6c5f3-2991-476b-81c7-c16f3c610ff5" xlink:href="agnc-20220331.xsd#agnc_TotalFairValueofSecuritiesPledgedandAccruedInterest"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_agnc_OffsettingAssetsAndLiabilitiesLineItems_c6e3d711-5e52-446d-803e-0575ccb4b554" xlink:to="loc_agnc_TotalFairValueofSecuritiesPledgedandAccruedInterest_58c6c5f3-2991-476b-81c7-c16f3c610ff5" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_TotalFairValueOfAgencySecuritiesPledgedAndAccruedInterest_d343c3ae-5963-4dcf-8ecb-7fcde4f0d66d" xlink:href="agnc-20220331.xsd#agnc_TotalFairValueOfAgencySecuritiesPledgedAndAccruedInterest"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_agnc_OffsettingAssetsAndLiabilitiesLineItems_c6e3d711-5e52-446d-803e-0575ccb4b554" xlink:to="loc_agnc_TotalFairValueOfAgencySecuritiesPledgedAndAccruedInterest_d343c3ae-5963-4dcf-8ecb-7fcde4f0d66d" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_SecuritiesOwnedAndPledgedAsCollateralFairValue_4f215f85-ef63-4c30-ba67-4cdc786a02b7" xlink:href="agnc-20220331.xsd#agnc_SecuritiesOwnedAndPledgedAsCollateralFairValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_agnc_OffsettingAssetsAndLiabilitiesLineItems_c6e3d711-5e52-446d-803e-0575ccb4b554" xlink:to="loc_agnc_SecuritiesOwnedAndPledgedAsCollateralFairValue_4f215f85-ef63-4c30-ba67-4cdc786a02b7" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_OffsettingAssetsAndLiabilitiesTable_9c6e2575-d7f0-4f6e-879c-e52ba5526dae" xlink:href="agnc-20220331.xsd#agnc_OffsettingAssetsAndLiabilitiesTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_agnc_OffsettingAssetsAndLiabilitiesLineItems_c6e3d711-5e52-446d-803e-0575ccb4b554" xlink:to="loc_agnc_OffsettingAssetsAndLiabilitiesTable_9c6e2575-d7f0-4f6e-879c-e52ba5526dae" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RestrictedCashAndCashEquivalentsCashAndCashEquivalentsAxis_b7ebd4fa-e8de-481f-9e2f-b965bc46d135" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_RestrictedCashAndCashEquivalentsCashAndCashEquivalentsAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_agnc_OffsettingAssetsAndLiabilitiesTable_9c6e2575-d7f0-4f6e-879c-e52ba5526dae" xlink:to="loc_us-gaap_RestrictedCashAndCashEquivalentsCashAndCashEquivalentsAxis_b7ebd4fa-e8de-481f-9e2f-b965bc46d135" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RestrictedCashAndCashEquivalentsCashAndCashEquivalentsMember_b7ebd4fa-e8de-481f-9e2f-b965bc46d135_default" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_RestrictedCashAndCashEquivalentsCashAndCashEquivalentsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_RestrictedCashAndCashEquivalentsCashAndCashEquivalentsAxis_b7ebd4fa-e8de-481f-9e2f-b965bc46d135" xlink:to="loc_us-gaap_RestrictedCashAndCashEquivalentsCashAndCashEquivalentsMember_b7ebd4fa-e8de-481f-9e2f-b965bc46d135_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RestrictedCashAndCashEquivalentsCashAndCashEquivalentsMember_21e0bd61-46ea-49da-a6db-c389de78c814" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_RestrictedCashAndCashEquivalentsCashAndCashEquivalentsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_RestrictedCashAndCashEquivalentsCashAndCashEquivalentsAxis_b7ebd4fa-e8de-481f-9e2f-b965bc46d135" xlink:to="loc_us-gaap_RestrictedCashAndCashEquivalentsCashAndCashEquivalentsMember_21e0bd61-46ea-49da-a6db-c389de78c814" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RepurchaseAgreementsMember_a17c66ee-3519-4358-8dea-c9c4896086da" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_RepurchaseAgreementsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_RestrictedCashAndCashEquivalentsCashAndCashEquivalentsMember_21e0bd61-46ea-49da-a6db-c389de78c814" xlink:to="loc_us-gaap_RepurchaseAgreementsMember_a17c66ee-3519-4358-8dea-c9c4896086da" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_UnderPrimeBrokerAgreementsMember_a4572168-a619-4ad2-908f-39efbcc15809" xlink:href="agnc-20220331.xsd#agnc_UnderPrimeBrokerAgreementsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_RestrictedCashAndCashEquivalentsCashAndCashEquivalentsMember_21e0bd61-46ea-49da-a6db-c389de78c814" xlink:to="loc_agnc_UnderPrimeBrokerAgreementsMember_a4572168-a619-4ad2-908f-39efbcc15809" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_ExcludingCashReceivedMember_6512c40a-0193-4a1f-9877-a2220323a06e" xlink:href="agnc-20220331.xsd#agnc_ExcludingCashReceivedMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_RestrictedCashAndCashEquivalentsCashAndCashEquivalentsMember_21e0bd61-46ea-49da-a6db-c389de78c814" xlink:to="loc_agnc_ExcludingCashReceivedMember_6512c40a-0193-4a1f-9877-a2220323a06e" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_DerivativeAgreementsAndOtherMember_a00cb5ea-d594-4055-a100-d02273c751d4" xlink:href="agnc-20220331.xsd#agnc_DerivativeAgreementsAndOtherMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_RestrictedCashAndCashEquivalentsCashAndCashEquivalentsMember_21e0bd61-46ea-49da-a6db-c389de78c814" xlink:to="loc_agnc_DerivativeAgreementsAndOtherMember_a00cb5ea-d594-4055-a100-d02273c751d4" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_UnderlyingAssetClassAxis_0b385382-f4e3-40f2-8adb-672593dfa16d" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_UnderlyingAssetClassAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_agnc_OffsettingAssetsAndLiabilitiesTable_9c6e2575-d7f0-4f6e-879c-e52ba5526dae" xlink:to="loc_us-gaap_UnderlyingAssetClassAxis_0b385382-f4e3-40f2-8adb-672593dfa16d" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_UnderlyingAssetClassDomain_0b385382-f4e3-40f2-8adb-672593dfa16d_default" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_UnderlyingAssetClassDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_UnderlyingAssetClassAxis_0b385382-f4e3-40f2-8adb-672593dfa16d" xlink:to="loc_us-gaap_UnderlyingAssetClassDomain_0b385382-f4e3-40f2-8adb-672593dfa16d_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_UnderlyingAssetClassDomain_da01b295-3e9b-47d0-9c86-3e8da718de33" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_UnderlyingAssetClassDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_UnderlyingAssetClassAxis_0b385382-f4e3-40f2-8adb-672593dfa16d" xlink:to="loc_us-gaap_UnderlyingAssetClassDomain_da01b295-3e9b-47d0-9c86-3e8da718de33" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RepurchaseAgreementsMember_ff64109e-024b-4cda-a76b-5beea8090aa6" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_RepurchaseAgreementsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_UnderlyingAssetClassDomain_da01b295-3e9b-47d0-9c86-3e8da718de33" xlink:to="loc_us-gaap_RepurchaseAgreementsMember_ff64109e-024b-4cda-a76b-5beea8090aa6" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_VariableInterestEntityPrimaryBeneficiaryMember_ea5d0494-1d43-4fd9-b329-8b0c9c5cc66e" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_VariableInterestEntityPrimaryBeneficiaryMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_UnderlyingAssetClassDomain_da01b295-3e9b-47d0-9c86-3e8da718de33" xlink:to="loc_us-gaap_VariableInterestEntityPrimaryBeneficiaryMember_ea5d0494-1d43-4fd9-b329-8b0c9c5cc66e" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_UnderPrimeBrokerAgreementsMember_f834cfd8-fea6-4a02-b627-3b186eb9e34e" xlink:href="agnc-20220331.xsd#agnc_UnderPrimeBrokerAgreementsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_UnderlyingAssetClassDomain_da01b295-3e9b-47d0-9c86-3e8da718de33" xlink:to="loc_agnc_UnderPrimeBrokerAgreementsMember_f834cfd8-fea6-4a02-b627-3b186eb9e34e" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_IncludesSoldButNotYetSettledSecuritiesMember_2b2217c4-47e5-433d-adf0-79e8431d62ff" xlink:href="agnc-20220331.xsd#agnc_IncludesSoldButNotYetSettledSecuritiesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_UnderlyingAssetClassDomain_da01b295-3e9b-47d0-9c86-3e8da718de33" xlink:to="loc_agnc_IncludesSoldButNotYetSettledSecuritiesMember_2b2217c4-47e5-433d-adf0-79e8431d62ff" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_CreditRiskTransferSecuritiesMember_78fbaa5e-dfde-43fd-9b7c-71b1bfebaada" xlink:href="agnc-20220331.xsd#agnc_CreditRiskTransferSecuritiesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_UnderlyingAssetClassDomain_da01b295-3e9b-47d0-9c86-3e8da718de33" xlink:to="loc_agnc_CreditRiskTransferSecuritiesMember_78fbaa5e-dfde-43fd-9b7c-71b1bfebaada" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_NonAgencyMember_d406098d-832c-4e7f-8d58-aad79bf1db3f" xlink:href="agnc-20220331.xsd#agnc_NonAgencyMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_UnderlyingAssetClassDomain_da01b295-3e9b-47d0-9c86-3e8da718de33" xlink:to="loc_agnc_NonAgencyMember_d406098d-832c-4e7f-8d58-aad79bf1db3f" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_AAANonAgencyMortgageBackedSecuritiesMember_c4a0a4b8-aedb-4f50-8fa7-fdea34b14f3b" xlink:href="agnc-20220331.xsd#agnc_AAANonAgencyMortgageBackedSecuritiesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_UnderlyingAssetClassDomain_da01b295-3e9b-47d0-9c86-3e8da718de33" xlink:to="loc_agnc_AAANonAgencyMortgageBackedSecuritiesMember_c4a0a4b8-aedb-4f50-8fa7-fdea34b14f3b" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_USTreasurySecuritiesMember_b85070c3-2ad0-43df-940e-6ad99794945d" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_USTreasurySecuritiesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_UnderlyingAssetClassDomain_da01b295-3e9b-47d0-9c86-3e8da718de33" xlink:to="loc_us-gaap_USTreasurySecuritiesMember_b85070c3-2ad0-43df-940e-6ad99794945d" xlink:type="arc" order="7"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DerivativeMember_dbbde79b-b570-415e-a090-ed167fbe7e03" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DerivativeMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_UnderlyingAssetClassDomain_da01b295-3e9b-47d0-9c86-3e8da718de33" xlink:to="loc_us-gaap_DerivativeMember_dbbde79b-b570-415e-a090-ed167fbe7e03" xlink:type="arc" order="8"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_USTreasurySecuritiesMember_1f158de8-54c0-422e-8615-4263f54a4bf8" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_USTreasurySecuritiesMember"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_DerivativeAgreementsAndOtherMember_ae7effbb-3525-49b8-aaab-7e2153cfaf25" xlink:href="agnc-20220331.xsd#agnc_DerivativeAgreementsAndOtherMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_UnderlyingAssetClassDomain_da01b295-3e9b-47d0-9c86-3e8da718de33" xlink:to="loc_agnc_DerivativeAgreementsAndOtherMember_ae7effbb-3525-49b8-aaab-7e2153cfaf25" xlink:type="arc" order="10"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_InvestmentTypeAxis_4bb433d1-0ef6-40af-9a14-c23c772af91d" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_InvestmentTypeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_agnc_OffsettingAssetsAndLiabilitiesTable_9c6e2575-d7f0-4f6e-879c-e52ba5526dae" xlink:to="loc_us-gaap_InvestmentTypeAxis_4bb433d1-0ef6-40af-9a14-c23c772af91d" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_InvestmentTypeCategorizationMember_4bb433d1-0ef6-40af-9a14-c23c772af91d_default" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_InvestmentTypeCategorizationMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_InvestmentTypeAxis_4bb433d1-0ef6-40af-9a14-c23c772af91d" xlink:to="loc_us-gaap_InvestmentTypeCategorizationMember_4bb433d1-0ef6-40af-9a14-c23c772af91d_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_InvestmentTypeCategorizationMember_59e10861-20c0-450c-a9d1-6ad109f9c8b4" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_InvestmentTypeCategorizationMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_InvestmentTypeAxis_4bb433d1-0ef6-40af-9a14-c23c772af91d" xlink:to="loc_us-gaap_InvestmentTypeCategorizationMember_59e10861-20c0-450c-a9d1-6ad109f9c8b4" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_UnderPrimeBrokerAgreementsMember_88dd028e-8161-4c65-8b3b-3d1faf27f6d4" xlink:href="agnc-20220331.xsd#agnc_UnderPrimeBrokerAgreementsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_InvestmentTypeCategorizationMember_59e10861-20c0-450c-a9d1-6ad109f9c8b4" xlink:to="loc_agnc_UnderPrimeBrokerAgreementsMember_88dd028e-8161-4c65-8b3b-3d1faf27f6d4" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RepurchaseAgreementsMember_af2b96b8-d1b5-4bcc-9bfd-6a9fed6795e7" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_RepurchaseAgreementsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_InvestmentTypeCategorizationMember_59e10861-20c0-450c-a9d1-6ad109f9c8b4" xlink:to="loc_us-gaap_RepurchaseAgreementsMember_af2b96b8-d1b5-4bcc-9bfd-6a9fed6795e7" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DerivativeMember_1df0f1b0-56ff-4126-b3a3-281ddf3e4f3b" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DerivativeMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_InvestmentTypeCategorizationMember_59e10861-20c0-450c-a9d1-6ad109f9c8b4" xlink:to="loc_us-gaap_DerivativeMember_1df0f1b0-56ff-4126-b3a3-281ddf3e4f3b" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_UnderPrimeBrokerAgreementsMember_91beee70-1e3c-4011-80b9-06491e5298ea" xlink:href="agnc-20220331.xsd#agnc_UnderPrimeBrokerAgreementsMember"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_DerivativeAgreementsAndOtherMember_0edfe233-7609-449e-a159-5592397aa521" xlink:href="agnc-20220331.xsd#agnc_DerivativeAgreementsAndOtherMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_InvestmentTypeCategorizationMember_59e10861-20c0-450c-a9d1-6ad109f9c8b4" xlink:to="loc_agnc_DerivativeAgreementsAndOtherMember_0edfe233-7609-449e-a159-5592397aa521" xlink:type="arc" order="4"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.agnc.com/role/PledgedAssetsSecuritiesPledgedasCollateralDetails" xlink:type="simple" xlink:href="agnc-20220331.xsd#PledgedAssetsSecuritiesPledgedasCollateralDetails"/>
  <link:definitionLink xlink:role="http://www.agnc.com/role/PledgedAssetsSecuritiesPledgedasCollateralDetails" xlink:type="extended" id="i69de51b96f674e75b9984a1842741b51_PledgedAssetsSecuritiesPledgedasCollateralDetails">
    <link:loc xlink:type="locator" xlink:label="loc_agnc_OffsettingAssetsAndLiabilitiesLineItems_1c8c0db7-c3d2-483e-b03e-92af13455d48" xlink:href="agnc-20220331.xsd#agnc_OffsettingAssetsAndLiabilitiesLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_RetainedInterestsinConsolidatedVIEsPledgedasCollateralUnderRepurchaseAgreements_fecec32a-5938-4f8b-b02d-e5d3506b509b" xlink:href="agnc-20220331.xsd#agnc_RetainedInterestsinConsolidatedVIEsPledgedasCollateralUnderRepurchaseAgreements"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_agnc_OffsettingAssetsAndLiabilitiesLineItems_1c8c0db7-c3d2-483e-b03e-92af13455d48" xlink:to="loc_agnc_RetainedInterestsinConsolidatedVIEsPledgedasCollateralUnderRepurchaseAgreements_fecec32a-5938-4f8b-b02d-e5d3506b509b" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_SecuritiesOwnedAndPledgedAsCollateralFairValue_9496723c-430d-445e-b3d6-0be30fe74644" xlink:href="agnc-20220331.xsd#agnc_SecuritiesOwnedAndPledgedAsCollateralFairValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_agnc_OffsettingAssetsAndLiabilitiesLineItems_1c8c0db7-c3d2-483e-b03e-92af13455d48" xlink:to="loc_agnc_SecuritiesOwnedAndPledgedAsCollateralFairValue_9496723c-430d-445e-b3d6-0be30fe74644" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_AgencySecuritiesPledgedAsCollateralAmortizedCost_72412ae3-c80c-4d94-a0c8-41f0bd3790f1" xlink:href="agnc-20220331.xsd#agnc_AgencySecuritiesPledgedAsCollateralAmortizedCost"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_agnc_OffsettingAssetsAndLiabilitiesLineItems_1c8c0db7-c3d2-483e-b03e-92af13455d48" xlink:to="loc_agnc_AgencySecuritiesPledgedAsCollateralAmortizedCost_72412ae3-c80c-4d94-a0c8-41f0bd3790f1" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_AgencySecuritiesPledgedAsCollateralAccruedInterest_ed96381e-c7fd-44cd-a015-00946af9c693" xlink:href="agnc-20220331.xsd#agnc_AgencySecuritiesPledgedAsCollateralAccruedInterest"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_agnc_OffsettingAssetsAndLiabilitiesLineItems_1c8c0db7-c3d2-483e-b03e-92af13455d48" xlink:to="loc_agnc_AgencySecuritiesPledgedAsCollateralAccruedInterest_ed96381e-c7fd-44cd-a015-00946af9c693" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CollateralSecuritiesRepledgedDeliveredOrUsed_4716559c-6cc8-484b-8f0f-1c8ec1ee40ce" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_CollateralSecuritiesRepledgedDeliveredOrUsed"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_agnc_OffsettingAssetsAndLiabilitiesLineItems_1c8c0db7-c3d2-483e-b03e-92af13455d48" xlink:to="loc_us-gaap_CollateralSecuritiesRepledgedDeliveredOrUsed_4716559c-6cc8-484b-8f0f-1c8ec1ee40ce" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_OffsettingAssetsAndLiabilitiesTable_be123737-c86b-4124-ab22-8c6c89037fe2" xlink:href="agnc-20220331.xsd#agnc_OffsettingAssetsAndLiabilitiesTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_agnc_OffsettingAssetsAndLiabilitiesLineItems_1c8c0db7-c3d2-483e-b03e-92af13455d48" xlink:to="loc_agnc_OffsettingAssetsAndLiabilitiesTable_be123737-c86b-4124-ab22-8c6c89037fe2" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_UnderlyingAssetClassAxis_c95c4fd9-ea2d-4288-a090-5df31a837877" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_UnderlyingAssetClassAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_agnc_OffsettingAssetsAndLiabilitiesTable_be123737-c86b-4124-ab22-8c6c89037fe2" xlink:to="loc_us-gaap_UnderlyingAssetClassAxis_c95c4fd9-ea2d-4288-a090-5df31a837877" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_UnderlyingAssetClassDomain_c95c4fd9-ea2d-4288-a090-5df31a837877_default" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_UnderlyingAssetClassDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_UnderlyingAssetClassAxis_c95c4fd9-ea2d-4288-a090-5df31a837877" xlink:to="loc_us-gaap_UnderlyingAssetClassDomain_c95c4fd9-ea2d-4288-a090-5df31a837877_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_UnderlyingAssetClassDomain_cecd5011-feff-4cfd-9165-5fedfc5e5e4f" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_UnderlyingAssetClassDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_UnderlyingAssetClassAxis_c95c4fd9-ea2d-4288-a090-5df31a837877" xlink:to="loc_us-gaap_UnderlyingAssetClassDomain_cecd5011-feff-4cfd-9165-5fedfc5e5e4f" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_CreditRiskTransferSecuritiesMember_fc804f00-8fdd-4571-b99a-aa7825b70429" xlink:href="agnc-20220331.xsd#agnc_CreditRiskTransferSecuritiesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_UnderlyingAssetClassDomain_cecd5011-feff-4cfd-9165-5fedfc5e5e4f" xlink:to="loc_agnc_CreditRiskTransferSecuritiesMember_fc804f00-8fdd-4571-b99a-aa7825b70429" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_USTreasurySecuritiesMember_5b30dd7e-f5d5-4862-a88a-af4e0599e47e" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_USTreasurySecuritiesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_UnderlyingAssetClassDomain_cecd5011-feff-4cfd-9165-5fedfc5e5e4f" xlink:to="loc_us-gaap_USTreasurySecuritiesMember_5b30dd7e-f5d5-4862-a88a-af4e0599e47e" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_NonAgencyMember_412661f2-4671-4e84-847d-9d75c23b9d1a" xlink:href="agnc-20220331.xsd#agnc_NonAgencyMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_UnderlyingAssetClassDomain_cecd5011-feff-4cfd-9165-5fedfc5e5e4f" xlink:to="loc_agnc_NonAgencyMember_412661f2-4671-4e84-847d-9d75c23b9d1a" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_InvestmentTypeAxis_ebb832d8-d5ce-4df8-9df6-4ca3be02740c" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_InvestmentTypeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_agnc_OffsettingAssetsAndLiabilitiesTable_be123737-c86b-4124-ab22-8c6c89037fe2" xlink:to="loc_us-gaap_InvestmentTypeAxis_ebb832d8-d5ce-4df8-9df6-4ca3be02740c" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_InvestmentTypeCategorizationMember_ebb832d8-d5ce-4df8-9df6-4ca3be02740c_default" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_InvestmentTypeCategorizationMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_InvestmentTypeAxis_ebb832d8-d5ce-4df8-9df6-4ca3be02740c" xlink:to="loc_us-gaap_InvestmentTypeCategorizationMember_ebb832d8-d5ce-4df8-9df6-4ca3be02740c_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_InvestmentTypeCategorizationMember_9ddb67c5-06fb-40ce-b0ed-7d78651b1f58" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_InvestmentTypeCategorizationMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_InvestmentTypeAxis_ebb832d8-d5ce-4df8-9df6-4ca3be02740c" xlink:to="loc_us-gaap_InvestmentTypeCategorizationMember_9ddb67c5-06fb-40ce-b0ed-7d78651b1f58" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RepurchaseAgreementsMember_298533a9-3291-4e45-8268-563b86847d0e" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_RepurchaseAgreementsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_InvestmentTypeCategorizationMember_9ddb67c5-06fb-40ce-b0ed-7d78651b1f58" xlink:to="loc_us-gaap_RepurchaseAgreementsMember_298533a9-3291-4e45-8268-563b86847d0e" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DerivativeMember_1cfe5eb0-1c61-434e-bf5c-02ef60af783a" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DerivativeMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_InvestmentTypeCategorizationMember_9ddb67c5-06fb-40ce-b0ed-7d78651b1f58" xlink:to="loc_us-gaap_DerivativeMember_1cfe5eb0-1c61-434e-bf5c-02ef60af783a" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AgencySecuritiesMember_cc3e0880-3b10-4ec5-8244-7b0071b450bf" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AgencySecuritiesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_InvestmentTypeCategorizationMember_9ddb67c5-06fb-40ce-b0ed-7d78651b1f58" xlink:to="loc_us-gaap_AgencySecuritiesMember_cc3e0880-3b10-4ec5-8244-7b0071b450bf" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_USTreasurySecuritiesMember_1f89af77-d164-4d7d-bb23-d7ea6f8aa6e1" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_USTreasurySecuritiesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_InvestmentTypeCategorizationMember_9ddb67c5-06fb-40ce-b0ed-7d78651b1f58" xlink:to="loc_us-gaap_USTreasurySecuritiesMember_1f89af77-d164-4d7d-bb23-d7ea6f8aa6e1" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AssetsSoldUnderAgreementsToRepurchaseMaturityPeriodsAxis_bea297c2-c6fa-4860-bcd4-e266edc8ee04" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AssetsSoldUnderAgreementsToRepurchaseMaturityPeriodsAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_agnc_OffsettingAssetsAndLiabilitiesTable_be123737-c86b-4124-ab22-8c6c89037fe2" xlink:to="loc_us-gaap_AssetsSoldUnderAgreementsToRepurchaseMaturityPeriodsAxis_bea297c2-c6fa-4860-bcd4-e266edc8ee04" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AssetsSoldUnderAgreementsToRepurchaseMaturityPeriodDomain_bea297c2-c6fa-4860-bcd4-e266edc8ee04_default" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AssetsSoldUnderAgreementsToRepurchaseMaturityPeriodDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_AssetsSoldUnderAgreementsToRepurchaseMaturityPeriodsAxis_bea297c2-c6fa-4860-bcd4-e266edc8ee04" xlink:to="loc_us-gaap_AssetsSoldUnderAgreementsToRepurchaseMaturityPeriodDomain_bea297c2-c6fa-4860-bcd4-e266edc8ee04_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AssetsSoldUnderAgreementsToRepurchaseMaturityPeriodDomain_83375f51-62bc-457a-a4c8-09d48a831b72" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AssetsSoldUnderAgreementsToRepurchaseMaturityPeriodDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_AssetsSoldUnderAgreementsToRepurchaseMaturityPeriodsAxis_bea297c2-c6fa-4860-bcd4-e266edc8ee04" xlink:to="loc_us-gaap_AssetsSoldUnderAgreementsToRepurchaseMaturityPeriodDomain_83375f51-62bc-457a-a4c8-09d48a831b72" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_MaturityUpTo30DaysMember_dac2fef3-7401-418e-bad8-27dd3e03947a" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_MaturityUpTo30DaysMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AssetsSoldUnderAgreementsToRepurchaseMaturityPeriodDomain_83375f51-62bc-457a-a4c8-09d48a831b72" xlink:to="loc_us-gaap_MaturityUpTo30DaysMember_dac2fef3-7401-418e-bad8-27dd3e03947a" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_Maturity31To59DaysMember_0eb0ff6d-ae3e-4b27-ba02-ba1d2df29cda" xlink:href="agnc-20220331.xsd#agnc_Maturity31To59DaysMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AssetsSoldUnderAgreementsToRepurchaseMaturityPeriodDomain_83375f51-62bc-457a-a4c8-09d48a831b72" xlink:to="loc_agnc_Maturity31To59DaysMember_0eb0ff6d-ae3e-4b27-ba02-ba1d2df29cda" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_Maturity60To90DaysMember_de61ac90-1925-4fe3-863b-4ffa8208e5af" xlink:href="agnc-20220331.xsd#agnc_Maturity60To90DaysMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AssetsSoldUnderAgreementsToRepurchaseMaturityPeriodDomain_83375f51-62bc-457a-a4c8-09d48a831b72" xlink:to="loc_agnc_Maturity60To90DaysMember_de61ac90-1925-4fe3-863b-4ffa8208e5af" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_MaturityOver90DaysMember_73f0744d-d4c4-426c-9f0c-b8ed78ec4dbb" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_MaturityOver90DaysMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AssetsSoldUnderAgreementsToRepurchaseMaturityPeriodDomain_83375f51-62bc-457a-a4c8-09d48a831b72" xlink:to="loc_us-gaap_MaturityOver90DaysMember_73f0744d-d4c4-426c-9f0c-b8ed78ec4dbb" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_A2Daysto1MonthMember_1c6b701d-341b-4b37-b350-d4443102bca4" xlink:href="agnc-20220331.xsd#agnc_A2Daysto1MonthMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AssetsSoldUnderAgreementsToRepurchaseMaturityPeriodDomain_83375f51-62bc-457a-a4c8-09d48a831b72" xlink:to="loc_agnc_A2Daysto1MonthMember_1c6b701d-341b-4b37-b350-d4443102bca4" xlink:type="arc" order="4"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.agnc.com/role/PledgedAssetsAssetsPledgedfromCounterpartiesDetails" xlink:type="simple" xlink:href="agnc-20220331.xsd#PledgedAssetsAssetsPledgedfromCounterpartiesDetails"/>
  <link:definitionLink xlink:role="http://www.agnc.com/role/PledgedAssetsAssetsPledgedfromCounterpartiesDetails" xlink:type="extended" id="i80accb51fc5347c3abe23db0fb9711fd_PledgedAssetsAssetsPledgedfromCounterpartiesDetails">
    <link:loc xlink:type="locator" xlink:label="loc_agnc_OffsettingAssetsAndLiabilitiesLineItems_775b6c4a-5c67-4a24-9261-7c19ba6b077a" xlink:href="agnc-20220331.xsd#agnc_OffsettingAssetsAndLiabilitiesLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_PledgedFinancialInstrumentsSecurities_5a62ae5c-562a-4a86-96c7-971e56b4d13d" xlink:href="agnc-20220331.xsd#agnc_PledgedFinancialInstrumentsSecurities"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_agnc_OffsettingAssetsAndLiabilitiesLineItems_775b6c4a-5c67-4a24-9261-7c19ba6b077a" xlink:to="loc_agnc_PledgedFinancialInstrumentsSecurities_5a62ae5c-562a-4a86-96c7-971e56b4d13d" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FederalHomeLoanBankStock_6e0d0b9b-b6b3-41ca-a558-63744a12e9b3" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FederalHomeLoanBankStock"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_agnc_OffsettingAssetsAndLiabilitiesLineItems_775b6c4a-5c67-4a24-9261-7c19ba6b077a" xlink:to="loc_us-gaap_FederalHomeLoanBankStock_6e0d0b9b-b6b3-41ca-a558-63744a12e9b3" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_ObligationToReturnSecuritiesBorrowedUnderReverseRepurchaseAgreementsAtFairValue_66463cf1-e8a2-4d27-a1c4-4b5b8ad9370a" xlink:href="agnc-20220331.xsd#agnc_ObligationToReturnSecuritiesBorrowedUnderReverseRepurchaseAgreementsAtFairValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_agnc_OffsettingAssetsAndLiabilitiesLineItems_775b6c4a-5c67-4a24-9261-7c19ba6b077a" xlink:to="loc_agnc_ObligationToReturnSecuritiesBorrowedUnderReverseRepurchaseAgreementsAtFairValue_66463cf1-e8a2-4d27-a1c4-4b5b8ad9370a" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RestrictedCashAndCashEquivalents_36cb370c-a1c6-4d4c-88ad-1f53d6a775a9" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_RestrictedCashAndCashEquivalents"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_agnc_OffsettingAssetsAndLiabilitiesLineItems_775b6c4a-5c67-4a24-9261-7c19ba6b077a" xlink:to="loc_us-gaap_RestrictedCashAndCashEquivalents_36cb370c-a1c6-4d4c-88ad-1f53d6a775a9" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_RestrictedCashandSecuritiesPledged_b1b26d6f-6840-429c-bae6-65704e20e22f" xlink:href="agnc-20220331.xsd#agnc_RestrictedCashandSecuritiesPledged"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_agnc_OffsettingAssetsAndLiabilitiesLineItems_775b6c4a-5c67-4a24-9261-7c19ba6b077a" xlink:to="loc_agnc_RestrictedCashandSecuritiesPledged_b1b26d6f-6840-429c-bae6-65704e20e22f" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CollateralSecuritiesRepledgedDeliveredOrUsed_0c55b83c-08ea-4c3f-b5ce-5d3579e5a347" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_CollateralSecuritiesRepledgedDeliveredOrUsed"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_agnc_OffsettingAssetsAndLiabilitiesLineItems_775b6c4a-5c67-4a24-9261-7c19ba6b077a" xlink:to="loc_us-gaap_CollateralSecuritiesRepledgedDeliveredOrUsed_0c55b83c-08ea-4c3f-b5ce-5d3579e5a347" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_OffsettingAssetsAndLiabilitiesTable_a2825830-658a-4fa9-9d58-f166526fadb8" xlink:href="agnc-20220331.xsd#agnc_OffsettingAssetsAndLiabilitiesTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_agnc_OffsettingAssetsAndLiabilitiesLineItems_775b6c4a-5c67-4a24-9261-7c19ba6b077a" xlink:to="loc_agnc_OffsettingAssetsAndLiabilitiesTable_a2825830-658a-4fa9-9d58-f166526fadb8" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RestrictedCashAndCashEquivalentsCashAndCashEquivalentsAxis_c99b3e6a-1ebb-46e7-a7af-c9a5ad6be8da" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_RestrictedCashAndCashEquivalentsCashAndCashEquivalentsAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_agnc_OffsettingAssetsAndLiabilitiesTable_a2825830-658a-4fa9-9d58-f166526fadb8" xlink:to="loc_us-gaap_RestrictedCashAndCashEquivalentsCashAndCashEquivalentsAxis_c99b3e6a-1ebb-46e7-a7af-c9a5ad6be8da" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RestrictedCashAndCashEquivalentsCashAndCashEquivalentsMember_c99b3e6a-1ebb-46e7-a7af-c9a5ad6be8da_default" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_RestrictedCashAndCashEquivalentsCashAndCashEquivalentsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_RestrictedCashAndCashEquivalentsCashAndCashEquivalentsAxis_c99b3e6a-1ebb-46e7-a7af-c9a5ad6be8da" xlink:to="loc_us-gaap_RestrictedCashAndCashEquivalentsCashAndCashEquivalentsMember_c99b3e6a-1ebb-46e7-a7af-c9a5ad6be8da_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RestrictedCashAndCashEquivalentsCashAndCashEquivalentsMember_f704ab49-fb60-4f3f-9a34-a1ef120550c2" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_RestrictedCashAndCashEquivalentsCashAndCashEquivalentsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_RestrictedCashAndCashEquivalentsCashAndCashEquivalentsAxis_c99b3e6a-1ebb-46e7-a7af-c9a5ad6be8da" xlink:to="loc_us-gaap_RestrictedCashAndCashEquivalentsCashAndCashEquivalentsMember_f704ab49-fb60-4f3f-9a34-a1ef120550c2" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DerivativeMember_36ac9606-a088-4dd8-be95-4045ea89254c" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DerivativeMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_RestrictedCashAndCashEquivalentsCashAndCashEquivalentsMember_f704ab49-fb60-4f3f-9a34-a1ef120550c2" xlink:to="loc_us-gaap_DerivativeMember_36ac9606-a088-4dd8-be95-4045ea89254c" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_InvestmentTypeAxis_f61cf2c8-3cbc-466f-a89e-d7d8cf4c06e8" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_InvestmentTypeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_agnc_OffsettingAssetsAndLiabilitiesTable_a2825830-658a-4fa9-9d58-f166526fadb8" xlink:to="loc_us-gaap_InvestmentTypeAxis_f61cf2c8-3cbc-466f-a89e-d7d8cf4c06e8" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_InvestmentTypeCategorizationMember_f61cf2c8-3cbc-466f-a89e-d7d8cf4c06e8_default" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_InvestmentTypeCategorizationMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_InvestmentTypeAxis_f61cf2c8-3cbc-466f-a89e-d7d8cf4c06e8" xlink:to="loc_us-gaap_InvestmentTypeCategorizationMember_f61cf2c8-3cbc-466f-a89e-d7d8cf4c06e8_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_InvestmentTypeCategorizationMember_81a43cea-b017-4c7a-91ae-a0b3757e2d18" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_InvestmentTypeCategorizationMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_InvestmentTypeAxis_f61cf2c8-3cbc-466f-a89e-d7d8cf4c06e8" xlink:to="loc_us-gaap_InvestmentTypeCategorizationMember_81a43cea-b017-4c7a-91ae-a0b3757e2d18" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_ReverseRepurchaseAgreementsMember_a02a44c5-90db-4e17-b928-5c2a9ea80475" xlink:href="agnc-20220331.xsd#agnc_ReverseRepurchaseAgreementsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_InvestmentTypeCategorizationMember_81a43cea-b017-4c7a-91ae-a0b3757e2d18" xlink:to="loc_agnc_ReverseRepurchaseAgreementsMember_a02a44c5-90db-4e17-b928-5c2a9ea80475" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DerivativeMember_f9962b26-2c72-4e7d-8adc-7aa693c83db8" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DerivativeMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_InvestmentTypeCategorizationMember_81a43cea-b017-4c7a-91ae-a0b3757e2d18" xlink:to="loc_us-gaap_DerivativeMember_f9962b26-2c72-4e7d-8adc-7aa693c83db8" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_UnderlyingAssetClassAxis_60724945-724a-409e-afbd-4109d0d09726" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_UnderlyingAssetClassAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_agnc_OffsettingAssetsAndLiabilitiesTable_a2825830-658a-4fa9-9d58-f166526fadb8" xlink:to="loc_us-gaap_UnderlyingAssetClassAxis_60724945-724a-409e-afbd-4109d0d09726" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_UnderlyingAssetClassDomain_60724945-724a-409e-afbd-4109d0d09726_default" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_UnderlyingAssetClassDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_UnderlyingAssetClassAxis_60724945-724a-409e-afbd-4109d0d09726" xlink:to="loc_us-gaap_UnderlyingAssetClassDomain_60724945-724a-409e-afbd-4109d0d09726_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_UnderlyingAssetClassDomain_a192f2c6-8d61-45d5-8aa2-706aa9c70e84" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_UnderlyingAssetClassDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_UnderlyingAssetClassAxis_60724945-724a-409e-afbd-4109d0d09726" xlink:to="loc_us-gaap_UnderlyingAssetClassDomain_a192f2c6-8d61-45d5-8aa2-706aa9c70e84" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_MortgageBackedSecuritiesIssuedByUSGovernmentSponsoredEnterprisesMember_aacfc8ba-b7d7-43d7-9aad-5fa9ebf85008" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_MortgageBackedSecuritiesIssuedByUSGovernmentSponsoredEnterprisesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_UnderlyingAssetClassDomain_a192f2c6-8d61-45d5-8aa2-706aa9c70e84" xlink:to="loc_us-gaap_MortgageBackedSecuritiesIssuedByUSGovernmentSponsoredEnterprisesMember_aacfc8ba-b7d7-43d7-9aad-5fa9ebf85008" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SecuritiesSoldUnderAgreementsToRepurchaseMember_d0ec25d7-7ab8-4292-812c-6464b33dac33" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_SecuritiesSoldUnderAgreementsToRepurchaseMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_UnderlyingAssetClassDomain_a192f2c6-8d61-45d5-8aa2-706aa9c70e84" xlink:to="loc_us-gaap_SecuritiesSoldUnderAgreementsToRepurchaseMember_d0ec25d7-7ab8-4292-812c-6464b33dac33" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DerivativeMember_46ecc930-8674-47e2-9c15-3a8164096cd8" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DerivativeMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_UnderlyingAssetClassDomain_a192f2c6-8d61-45d5-8aa2-706aa9c70e84" xlink:to="loc_us-gaap_DerivativeMember_46ecc930-8674-47e2-9c15-3a8164096cd8" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_USTreasurySecuritiesMember_c571f938-4187-40e9-87ca-558c273dc713" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_USTreasurySecuritiesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_UnderlyingAssetClassDomain_a192f2c6-8d61-45d5-8aa2-706aa9c70e84" xlink:to="loc_us-gaap_USTreasurySecuritiesMember_c571f938-4187-40e9-87ca-558c273dc713" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_ReverseRepurchaseAgreementsMember_e56a2f45-6663-46c5-8b64-fa832efe1cb3" xlink:href="agnc-20220331.xsd#agnc_ReverseRepurchaseAgreementsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_UnderlyingAssetClassDomain_a192f2c6-8d61-45d5-8aa2-706aa9c70e84" xlink:to="loc_agnc_ReverseRepurchaseAgreementsMember_e56a2f45-6663-46c5-8b64-fa832efe1cb3" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FinancialInstrumentAxis_9834c674-00ca-4a6f-aac8-abdb9f27aa61" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FinancialInstrumentAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_agnc_OffsettingAssetsAndLiabilitiesTable_a2825830-658a-4fa9-9d58-f166526fadb8" xlink:to="loc_us-gaap_FinancialInstrumentAxis_9834c674-00ca-4a6f-aac8-abdb9f27aa61" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_9834c674-00ca-4a6f-aac8-abdb9f27aa61_default" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_FinancialInstrumentAxis_9834c674-00ca-4a6f-aac8-abdb9f27aa61" xlink:to="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_9834c674-00ca-4a6f-aac8-abdb9f27aa61_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_fdd24166-dc87-415b-b878-c705ab7f0dc2" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_FinancialInstrumentAxis_9834c674-00ca-4a6f-aac8-abdb9f27aa61" xlink:to="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_fdd24166-dc87-415b-b878-c705ab7f0dc2" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_AssetsPledgedtoUsMember_ce417e1c-5950-4024-af1b-117dbc8a9f64" xlink:href="agnc-20220331.xsd#agnc_AssetsPledgedtoUsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_fdd24166-dc87-415b-b878-c705ab7f0dc2" xlink:to="loc_agnc_AssetsPledgedtoUsMember_ce417e1c-5950-4024-af1b-117dbc8a9f64" xlink:type="arc" order="0"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.agnc.com/role/PledgedAssetsOffsettingAssetsandLiabilitiesDetails" xlink:type="simple" xlink:href="agnc-20220331.xsd#PledgedAssetsOffsettingAssetsandLiabilitiesDetails"/>
  <link:definitionLink xlink:role="http://www.agnc.com/role/PledgedAssetsOffsettingAssetsandLiabilitiesDetails" xlink:type="extended" id="i833b8fb941ed45d0b538ba05e02c5f0d_PledgedAssetsOffsettingAssetsandLiabilitiesDetails">
    <link:loc xlink:type="locator" xlink:label="loc_agnc_OffsettingAssetsAndLiabilitiesLineItems_84b6dc0a-3efc-47df-9a16-8d88e1863aef" xlink:href="agnc-20220331.xsd#agnc_OffsettingAssetsAndLiabilitiesLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_GrossAmountOfRecognizedAssetsLiabilities_89da8b00-173d-4e8e-88ca-9b40f11c10d0" xlink:href="agnc-20220331.xsd#agnc_GrossAmountOfRecognizedAssetsLiabilities"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_agnc_OffsettingAssetsAndLiabilitiesLineItems_84b6dc0a-3efc-47df-9a16-8d88e1863aef" xlink:to="loc_agnc_GrossAmountOfRecognizedAssetsLiabilities_89da8b00-173d-4e8e-88ca-9b40f11c10d0" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_GrossAmountOffsetintheConsolidatedBalanceSheets_1d6c83b5-92e9-4ecd-b423-5c622ebf5b33" xlink:href="agnc-20220331.xsd#agnc_GrossAmountOffsetintheConsolidatedBalanceSheets"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_agnc_OffsettingAssetsAndLiabilitiesLineItems_84b6dc0a-3efc-47df-9a16-8d88e1863aef" xlink:to="loc_agnc_GrossAmountOffsetintheConsolidatedBalanceSheets_1d6c83b5-92e9-4ecd-b423-5c622ebf5b33" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_NetAmountofAssetsLiabilitiesPresentedontheBalanceSheet_a7435e58-df0b-4372-9d5c-35f360eee2cc" xlink:href="agnc-20220331.xsd#agnc_NetAmountofAssetsLiabilitiesPresentedontheBalanceSheet"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_agnc_OffsettingAssetsAndLiabilitiesLineItems_84b6dc0a-3efc-47df-9a16-8d88e1863aef" xlink:to="loc_agnc_NetAmountofAssetsLiabilitiesPresentedontheBalanceSheet_a7435e58-df0b-4372-9d5c-35f360eee2cc" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_GrossAmountsofFinancialInstrumentsNotOffsetontheBalanceSheet_45cb42bc-236b-49f6-8b56-03d3ad404b2d" xlink:href="agnc-20220331.xsd#agnc_GrossAmountsofFinancialInstrumentsNotOffsetontheBalanceSheet"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_agnc_OffsettingAssetsAndLiabilitiesLineItems_84b6dc0a-3efc-47df-9a16-8d88e1863aef" xlink:to="loc_agnc_GrossAmountsofFinancialInstrumentsNotOffsetontheBalanceSheet_45cb42bc-236b-49f6-8b56-03d3ad404b2d" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_GrossAmountsofCashCollateralNotOffsetontheBalanceSheet_512c3c7d-6275-46d0-aae4-55dc33a11ca3" xlink:href="agnc-20220331.xsd#agnc_GrossAmountsofCashCollateralNotOffsetontheBalanceSheet"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_agnc_OffsettingAssetsAndLiabilitiesLineItems_84b6dc0a-3efc-47df-9a16-8d88e1863aef" xlink:to="loc_agnc_GrossAmountsofCashCollateralNotOffsetontheBalanceSheet_512c3c7d-6275-46d0-aae4-55dc33a11ca3" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_NetAmountAfterDeductingGrossAmountsNotOffsetontheBalanceSheetFromNetAmountofAssetsLiabilitiesPresentedontheBalanceSheet_f16591e4-74c1-4b56-8881-03988a7ddf1c" xlink:href="agnc-20220331.xsd#agnc_NetAmountAfterDeductingGrossAmountsNotOffsetontheBalanceSheetFromNetAmountofAssetsLiabilitiesPresentedontheBalanceSheet"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_agnc_OffsettingAssetsAndLiabilitiesLineItems_84b6dc0a-3efc-47df-9a16-8d88e1863aef" xlink:to="loc_agnc_NetAmountAfterDeductingGrossAmountsNotOffsetontheBalanceSheetFromNetAmountofAssetsLiabilitiesPresentedontheBalanceSheet_f16591e4-74c1-4b56-8881-03988a7ddf1c" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_OffsettingAssetsAndLiabilitiesTable_c1083a4f-0fe1-4c83-bf0b-558e6f180971" xlink:href="agnc-20220331.xsd#agnc_OffsettingAssetsAndLiabilitiesTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_agnc_OffsettingAssetsAndLiabilitiesLineItems_84b6dc0a-3efc-47df-9a16-8d88e1863aef" xlink:to="loc_agnc_OffsettingAssetsAndLiabilitiesTable_c1083a4f-0fe1-4c83-bf0b-558e6f180971" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_BalanceSheetLocationAxis_e6757967-5739-4cee-a57a-40179ecc0dab" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_BalanceSheetLocationAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_agnc_OffsettingAssetsAndLiabilitiesTable_c1083a4f-0fe1-4c83-bf0b-558e6f180971" xlink:to="loc_us-gaap_BalanceSheetLocationAxis_e6757967-5739-4cee-a57a-40179ecc0dab" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_BalanceSheetLocationDomain_e6757967-5739-4cee-a57a-40179ecc0dab_default" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_BalanceSheetLocationDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_BalanceSheetLocationAxis_e6757967-5739-4cee-a57a-40179ecc0dab" xlink:to="loc_us-gaap_BalanceSheetLocationDomain_e6757967-5739-4cee-a57a-40179ecc0dab_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_BalanceSheetLocationDomain_77f52460-40b6-466c-8e9b-3bbbb5daae70" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_BalanceSheetLocationDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_BalanceSheetLocationAxis_e6757967-5739-4cee-a57a-40179ecc0dab" xlink:to="loc_us-gaap_BalanceSheetLocationDomain_77f52460-40b6-466c-8e9b-3bbbb5daae70" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_ReverseRepurchaseAgreementsMember_ebdc5e4d-0b90-4adf-8854-a69eab94da83" xlink:href="agnc-20220331.xsd#agnc_ReverseRepurchaseAgreementsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BalanceSheetLocationDomain_77f52460-40b6-466c-8e9b-3bbbb5daae70" xlink:to="loc_agnc_ReverseRepurchaseAgreementsMember_ebdc5e4d-0b90-4adf-8854-a69eab94da83" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RepurchaseAgreementsMember_127b7d06-2190-4bcb-8374-faa794b6f881" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_RepurchaseAgreementsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BalanceSheetLocationDomain_77f52460-40b6-466c-8e9b-3bbbb5daae70" xlink:to="loc_us-gaap_RepurchaseAgreementsMember_127b7d06-2190-4bcb-8374-faa794b6f881" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueByAssetClassAxis_3139bf03-3894-4bd4-b186-c77bd1ea9c51" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FairValueByAssetClassAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_agnc_OffsettingAssetsAndLiabilitiesTable_c1083a4f-0fe1-4c83-bf0b-558e6f180971" xlink:to="loc_us-gaap_FairValueByAssetClassAxis_3139bf03-3894-4bd4-b186-c77bd1ea9c51" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueAssetsMeasuredOnRecurringBasisUnobservableInputReconciliationByAssetClassDomain_3139bf03-3894-4bd4-b186-c77bd1ea9c51_default" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FairValueAssetsMeasuredOnRecurringBasisUnobservableInputReconciliationByAssetClassDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_FairValueByAssetClassAxis_3139bf03-3894-4bd4-b186-c77bd1ea9c51" xlink:to="loc_us-gaap_FairValueAssetsMeasuredOnRecurringBasisUnobservableInputReconciliationByAssetClassDomain_3139bf03-3894-4bd4-b186-c77bd1ea9c51_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueAssetsMeasuredOnRecurringBasisUnobservableInputReconciliationByAssetClassDomain_a94992a3-f0c1-4193-9a95-1ac5ced1def1" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FairValueAssetsMeasuredOnRecurringBasisUnobservableInputReconciliationByAssetClassDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_FairValueByAssetClassAxis_3139bf03-3894-4bd4-b186-c77bd1ea9c51" xlink:to="loc_us-gaap_FairValueAssetsMeasuredOnRecurringBasisUnobservableInputReconciliationByAssetClassDomain_a94992a3-f0c1-4193-9a95-1ac5ced1def1" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AssetsMember_4e5bc2ab-b0fc-41c7-81da-902cda60b914" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AssetsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FairValueAssetsMeasuredOnRecurringBasisUnobservableInputReconciliationByAssetClassDomain_a94992a3-f0c1-4193-9a95-1ac5ced1def1" xlink:to="loc_us-gaap_AssetsMember_4e5bc2ab-b0fc-41c7-81da-902cda60b914" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LiabilityMember_4bb533ad-bb4a-45c1-b646-1367edea4b27" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_LiabilityMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FairValueAssetsMeasuredOnRecurringBasisUnobservableInputReconciliationByAssetClassDomain_a94992a3-f0c1-4193-9a95-1ac5ced1def1" xlink:to="loc_us-gaap_LiabilityMember_4bb533ad-bb4a-45c1-b646-1367edea4b27" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DerivativeInstrumentRiskAxis_e5baad8b-c41a-4edb-b1ae-c162ea20e4af" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DerivativeInstrumentRiskAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_agnc_OffsettingAssetsAndLiabilitiesTable_c1083a4f-0fe1-4c83-bf0b-558e6f180971" xlink:to="loc_us-gaap_DerivativeInstrumentRiskAxis_e5baad8b-c41a-4edb-b1ae-c162ea20e4af" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DerivativeContractTypeDomain_e5baad8b-c41a-4edb-b1ae-c162ea20e4af_default" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DerivativeContractTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_DerivativeInstrumentRiskAxis_e5baad8b-c41a-4edb-b1ae-c162ea20e4af" xlink:to="loc_us-gaap_DerivativeContractTypeDomain_e5baad8b-c41a-4edb-b1ae-c162ea20e4af_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DerivativeContractTypeDomain_b2a2f787-6e42-4fd9-9410-c6b6065d52c5" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DerivativeContractTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_DerivativeInstrumentRiskAxis_e5baad8b-c41a-4edb-b1ae-c162ea20e4af" xlink:to="loc_us-gaap_DerivativeContractTypeDomain_b2a2f787-6e42-4fd9-9410-c6b6065d52c5" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_InterestRateSwapMember_cb8a2717-4b6b-4b12-96df-533b9a08cbdb" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_InterestRateSwapMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DerivativeContractTypeDomain_b2a2f787-6e42-4fd9-9410-c6b6065d52c5" xlink:to="loc_us-gaap_InterestRateSwapMember_cb8a2717-4b6b-4b12-96df-533b9a08cbdb" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RepurchaseAgreementsMember_8b3615cd-faab-4ff7-a3b9-0c27715b9309" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_RepurchaseAgreementsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DerivativeContractTypeDomain_b2a2f787-6e42-4fd9-9410-c6b6065d52c5" xlink:to="loc_us-gaap_RepurchaseAgreementsMember_8b3615cd-faab-4ff7-a3b9-0c27715b9309" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SwaptionMember_e3d8a3c4-d3c9-42fb-8325-afe7f51fb078" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_SwaptionMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DerivativeContractTypeDomain_b2a2f787-6e42-4fd9-9410-c6b6065d52c5" xlink:to="loc_us-gaap_SwaptionMember_e3d8a3c4-d3c9-42fb-8325-afe7f51fb078" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_TBAAndForwardSettlingSecuritiesMember_da1e0eec-d8bb-47fc-90cd-b13aab731297" xlink:href="agnc-20220331.xsd#agnc_TBAAndForwardSettlingSecuritiesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DerivativeContractTypeDomain_b2a2f787-6e42-4fd9-9410-c6b6065d52c5" xlink:to="loc_agnc_TBAAndForwardSettlingSecuritiesMember_da1e0eec-d8bb-47fc-90cd-b13aab731297" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_ReverseRepurchaseAgreementsMember_2a899d7c-a8b4-4500-9ee4-3eefaa14795a" xlink:href="agnc-20220331.xsd#agnc_ReverseRepurchaseAgreementsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DerivativeContractTypeDomain_b2a2f787-6e42-4fd9-9410-c6b6065d52c5" xlink:to="loc_agnc_ReverseRepurchaseAgreementsMember_2a899d7c-a8b4-4500-9ee4-3eefaa14795a" xlink:type="arc" order="4"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.agnc.com/role/FairValueMeasurementsDetails" xlink:type="simple" xlink:href="agnc-20220331.xsd#FairValueMeasurementsDetails"/>
  <link:definitionLink xlink:role="http://www.agnc.com/role/FairValueMeasurementsDetails" xlink:type="extended" id="i1484d36cf432468aa9c1ccad6251ed31_FairValueMeasurementsDetails">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems_a30665b4-15c2-41c7-9afa-2fd0f50832d8" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SecuritiesLoanedOrSoldUnderAgreementsToRepurchaseFairValueDisclosure_85937e85-7c5f-46f8-b9a3-53097ba440d3" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_SecuritiesLoanedOrSoldUnderAgreementsToRepurchaseFairValueDisclosure"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems_a30665b4-15c2-41c7-9afa-2fd0f50832d8" xlink:to="loc_us-gaap_SecuritiesLoanedOrSoldUnderAgreementsToRepurchaseFairValueDisclosure_85937e85-7c5f-46f8-b9a3-53097ba440d3" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SecuritiesSoldUnderAgreementsToRepurchase_4310beb4-9f91-45cd-ad50-8fa726557097" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_SecuritiesSoldUnderAgreementsToRepurchase"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems_a30665b4-15c2-41c7-9afa-2fd0f50832d8" xlink:to="loc_us-gaap_SecuritiesSoldUnderAgreementsToRepurchase_4310beb4-9f91-45cd-ad50-8fa726557097" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_TransfersBetweenHierarchyLevels_144111eb-afff-4cee-94fb-b3f18d58127c" xlink:href="agnc-20220331.xsd#agnc_TransfersBetweenHierarchyLevels"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems_a30665b4-15c2-41c7-9afa-2fd0f50832d8" xlink:to="loc_agnc_TransfersBetweenHierarchyLevels_144111eb-afff-4cee-94fb-b3f18d58127c" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FinancialInstrumentsOwnedMortgagesMortgageBackedAndAssetBackedSecuritiesAtFairValue_1a924be0-7603-4da4-bb39-09f0fc6c5ef2" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FinancialInstrumentsOwnedMortgagesMortgageBackedAndAssetBackedSecuritiesAtFairValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems_a30665b4-15c2-41c7-9afa-2fd0f50832d8" xlink:to="loc_us-gaap_FinancialInstrumentsOwnedMortgagesMortgageBackedAndAssetBackedSecuritiesAtFairValue_1a924be0-7603-4da4-bb39-09f0fc6c5ef2" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_NonAgencySecuritiesatFairValue_a48d3236-053f-4931-8780-83c809be24d3" xlink:href="agnc-20220331.xsd#agnc_NonAgencySecuritiesatFairValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems_a30665b4-15c2-41c7-9afa-2fd0f50832d8" xlink:to="loc_agnc_NonAgencySecuritiesatFairValue_a48d3236-053f-4931-8780-83c809be24d3" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FinancialInstrumentsOwnedOtherAtFairValue_4e97bf60-6c44-4dc1-a8c0-734552a2ca38" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FinancialInstrumentsOwnedOtherAtFairValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems_a30665b4-15c2-41c7-9afa-2fd0f50832d8" xlink:to="loc_us-gaap_FinancialInstrumentsOwnedOtherAtFairValue_4e97bf60-6c44-4dc1-a8c0-734552a2ca38" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FinancialInstrumentsOwnedUSGovernmentAndAgencyObligationsAtFairValue_9d592b1f-e7a4-4560-bff3-a60cac1261af" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FinancialInstrumentsOwnedUSGovernmentAndAgencyObligationsAtFairValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems_a30665b4-15c2-41c7-9afa-2fd0f50832d8" xlink:to="loc_us-gaap_FinancialInstrumentsOwnedUSGovernmentAndAgencyObligationsAtFairValue_9d592b1f-e7a4-4560-bff3-a60cac1261af" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EquitySecuritiesFvNi_1d12231c-be4d-4606-a33b-4833f1d39c25" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_EquitySecuritiesFvNi"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems_a30665b4-15c2-41c7-9afa-2fd0f50832d8" xlink:to="loc_us-gaap_EquitySecuritiesFvNi_1d12231c-be4d-4606-a33b-4833f1d39c25" xlink:type="arc" order="7"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DerivativeAssets_4d325eb8-7427-4587-8cf0-5713460eb518" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DerivativeAssets"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems_a30665b4-15c2-41c7-9afa-2fd0f50832d8" xlink:to="loc_us-gaap_DerivativeAssets_4d325eb8-7427-4587-8cf0-5713460eb518" xlink:type="arc" order="8"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DerivativeLiabilities_6abf1d43-3bfe-46f5-8bcd-8815d8e1bd87" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DerivativeLiabilities"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems_a30665b4-15c2-41c7-9afa-2fd0f50832d8" xlink:to="loc_us-gaap_DerivativeLiabilities_6abf1d43-3bfe-46f5-8bcd-8815d8e1bd87" xlink:type="arc" order="9"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AssetsFairValueDisclosure_3a52a227-f15e-43bb-bc43-c238b8263c11" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AssetsFairValueDisclosure"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems_a30665b4-15c2-41c7-9afa-2fd0f50832d8" xlink:to="loc_us-gaap_AssetsFairValueDisclosure_3a52a227-f15e-43bb-bc43-c238b8263c11" xlink:type="arc" order="10"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherLongTermDebt_ac5da0cc-9e74-45f2-a3f2-097133b39e51" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_OtherLongTermDebt"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems_a30665b4-15c2-41c7-9afa-2fd0f50832d8" xlink:to="loc_us-gaap_OtherLongTermDebt_ac5da0cc-9e74-45f2-a3f2-097133b39e51" xlink:type="arc" order="11"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_ObligationToReturnSecuritiesBorrowedUnderReverseRepurchaseAgreementsAtFairValue_5fa2765d-2f3e-4380-a435-a696ff4791c0" xlink:href="agnc-20220331.xsd#agnc_ObligationToReturnSecuritiesBorrowedUnderReverseRepurchaseAgreementsAtFairValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems_a30665b4-15c2-41c7-9afa-2fd0f50832d8" xlink:to="loc_agnc_ObligationToReturnSecuritiesBorrowedUnderReverseRepurchaseAgreementsAtFairValue_5fa2765d-2f3e-4380-a435-a696ff4791c0" xlink:type="arc" order="12"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DerivativeInstrumentsNotDesignatedAsHedgingInstrumentsAssetAtFairValue_bdf294cb-c2ce-428e-acda-0af8fe73a491" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DerivativeInstrumentsNotDesignatedAsHedgingInstrumentsAssetAtFairValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems_a30665b4-15c2-41c7-9afa-2fd0f50832d8" xlink:to="loc_us-gaap_DerivativeInstrumentsNotDesignatedAsHedgingInstrumentsAssetAtFairValue_bdf294cb-c2ce-428e-acda-0af8fe73a491" xlink:type="arc" order="13"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LiabilitiesFairValueDisclosure_9176ab55-7405-4cf2-8eb3-977f55aa06c8" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_LiabilitiesFairValueDisclosure"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems_a30665b4-15c2-41c7-9afa-2fd0f50832d8" xlink:to="loc_us-gaap_LiabilitiesFairValueDisclosure_9176ab55-7405-4cf2-8eb3-977f55aa06c8" xlink:type="arc" order="14"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable_ef66d1bd-6879-4404-ace6-173d85a73610" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems_a30665b4-15c2-41c7-9afa-2fd0f50832d8" xlink:to="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable_ef66d1bd-6879-4404-ace6-173d85a73610" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DerivativeInstrumentRiskAxis_ddf47de2-260f-46a2-b322-e37b59350740" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DerivativeInstrumentRiskAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable_ef66d1bd-6879-4404-ace6-173d85a73610" xlink:to="loc_us-gaap_DerivativeInstrumentRiskAxis_ddf47de2-260f-46a2-b322-e37b59350740" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DerivativeContractTypeDomain_ddf47de2-260f-46a2-b322-e37b59350740_default" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DerivativeContractTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_DerivativeInstrumentRiskAxis_ddf47de2-260f-46a2-b322-e37b59350740" xlink:to="loc_us-gaap_DerivativeContractTypeDomain_ddf47de2-260f-46a2-b322-e37b59350740_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DerivativeContractTypeDomain_ea6bb220-6a46-423a-a66a-b61518973d33" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DerivativeContractTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_DerivativeInstrumentRiskAxis_ddf47de2-260f-46a2-b322-e37b59350740" xlink:to="loc_us-gaap_DerivativeContractTypeDomain_ea6bb220-6a46-423a-a66a-b61518973d33" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FutureMember_2718ac29-322c-4fe6-9e94-b2f00ed944b6" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FutureMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DerivativeContractTypeDomain_ea6bb220-6a46-423a-a66a-b61518973d33" xlink:to="loc_us-gaap_FutureMember_2718ac29-322c-4fe6-9e94-b2f00ed944b6" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_USTreasurySecuritiesMember_c24398ed-0272-4d30-97d5-fb3ed64c366d" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_USTreasurySecuritiesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DerivativeContractTypeDomain_ea6bb220-6a46-423a-a66a-b61518973d33" xlink:to="loc_us-gaap_USTreasurySecuritiesMember_c24398ed-0272-4d30-97d5-fb3ed64c366d" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_InterestRateSwaptionMember_7ee416d3-9f81-44c8-821a-514f000d2fe8" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_InterestRateSwaptionMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DerivativeContractTypeDomain_ea6bb220-6a46-423a-a66a-b61518973d33" xlink:to="loc_us-gaap_InterestRateSwaptionMember_7ee416d3-9f81-44c8-821a-514f000d2fe8" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_InterestRateSwapMember_a280a117-925c-4602-98b9-79273b9e65b7" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_InterestRateSwapMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DerivativeContractTypeDomain_ea6bb220-6a46-423a-a66a-b61518973d33" xlink:to="loc_us-gaap_InterestRateSwapMember_a280a117-925c-4602-98b9-79273b9e65b7" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_PurchasesOfTBAsAndForwardSettlingSecuritiesMember_879dd34d-e3fe-47aa-9ccf-1b0b8f226e6c" xlink:href="agnc-20220331.xsd#agnc_PurchasesOfTBAsAndForwardSettlingSecuritiesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DerivativeContractTypeDomain_ea6bb220-6a46-423a-a66a-b61518973d33" xlink:to="loc_agnc_PurchasesOfTBAsAndForwardSettlingSecuritiesMember_879dd34d-e3fe-47aa-9ccf-1b0b8f226e6c" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DerivativeContractTypeDomain_c75d8a6b-65d7-4d9f-b782-0ad303586353" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DerivativeContractTypeDomain"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_BalanceSheetLocationAxis_cf910efb-9bc9-4b01-8c62-e3f65b84dcff" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_BalanceSheetLocationAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable_ef66d1bd-6879-4404-ace6-173d85a73610" xlink:to="loc_us-gaap_BalanceSheetLocationAxis_cf910efb-9bc9-4b01-8c62-e3f65b84dcff" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_BalanceSheetLocationDomain_cf910efb-9bc9-4b01-8c62-e3f65b84dcff_default" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_BalanceSheetLocationDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_BalanceSheetLocationAxis_cf910efb-9bc9-4b01-8c62-e3f65b84dcff" xlink:to="loc_us-gaap_BalanceSheetLocationDomain_cf910efb-9bc9-4b01-8c62-e3f65b84dcff_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_BalanceSheetLocationDomain_a71e6535-0b20-475a-a45d-6d9cc440fce3" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_BalanceSheetLocationDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_BalanceSheetLocationAxis_cf910efb-9bc9-4b01-8c62-e3f65b84dcff" xlink:to="loc_us-gaap_BalanceSheetLocationDomain_a71e6535-0b20-475a-a45d-6d9cc440fce3" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DerivativeFinancialInstrumentsLiabilitiesMember_7b9ceb71-63fb-451c-86de-6f79fe4a6eb3" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DerivativeFinancialInstrumentsLiabilitiesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BalanceSheetLocationDomain_a71e6535-0b20-475a-a45d-6d9cc440fce3" xlink:to="loc_us-gaap_DerivativeFinancialInstrumentsLiabilitiesMember_7b9ceb71-63fb-451c-86de-6f79fe4a6eb3" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueByMeasurementFrequencyAxis_861d9016-77bd-42a3-a7d0-178c62ae7503" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FairValueByMeasurementFrequencyAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable_ef66d1bd-6879-4404-ace6-173d85a73610" xlink:to="loc_us-gaap_FairValueByMeasurementFrequencyAxis_861d9016-77bd-42a3-a7d0-178c62ae7503" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueMeasurementFrequencyDomain_861d9016-77bd-42a3-a7d0-178c62ae7503_default" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FairValueMeasurementFrequencyDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_FairValueByMeasurementFrequencyAxis_861d9016-77bd-42a3-a7d0-178c62ae7503" xlink:to="loc_us-gaap_FairValueMeasurementFrequencyDomain_861d9016-77bd-42a3-a7d0-178c62ae7503_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueMeasurementFrequencyDomain_fe01b4b4-812c-45ca-a347-fc20e98dc626" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FairValueMeasurementFrequencyDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_FairValueByMeasurementFrequencyAxis_861d9016-77bd-42a3-a7d0-178c62ae7503" xlink:to="loc_us-gaap_FairValueMeasurementFrequencyDomain_fe01b4b4-812c-45ca-a347-fc20e98dc626" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueMeasurementsRecurringMember_12d3cc18-7ca2-4f96-ba69-41301ec00001" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FairValueMeasurementsRecurringMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FairValueMeasurementFrequencyDomain_fe01b4b4-812c-45ca-a347-fc20e98dc626" xlink:to="loc_us-gaap_FairValueMeasurementsRecurringMember_12d3cc18-7ca2-4f96-ba69-41301ec00001" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueByFairValueHierarchyLevelAxis_36dfac11-8e6d-4a37-ade7-d63ff9f12fa7" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FairValueByFairValueHierarchyLevelAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable_ef66d1bd-6879-4404-ace6-173d85a73610" xlink:to="loc_us-gaap_FairValueByFairValueHierarchyLevelAxis_36dfac11-8e6d-4a37-ade7-d63ff9f12fa7" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueMeasurementsFairValueHierarchyDomain_36dfac11-8e6d-4a37-ade7-d63ff9f12fa7_default" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FairValueMeasurementsFairValueHierarchyDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_FairValueByFairValueHierarchyLevelAxis_36dfac11-8e6d-4a37-ade7-d63ff9f12fa7" xlink:to="loc_us-gaap_FairValueMeasurementsFairValueHierarchyDomain_36dfac11-8e6d-4a37-ade7-d63ff9f12fa7_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueMeasurementsFairValueHierarchyDomain_74b1c213-872a-4f3a-8e8a-cda92885a315" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FairValueMeasurementsFairValueHierarchyDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_FairValueByFairValueHierarchyLevelAxis_36dfac11-8e6d-4a37-ade7-d63ff9f12fa7" xlink:to="loc_us-gaap_FairValueMeasurementsFairValueHierarchyDomain_74b1c213-872a-4f3a-8e8a-cda92885a315" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueInputsLevel1Member_e663a4a7-96d9-425e-a173-45b7ae646e23" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FairValueInputsLevel1Member"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FairValueMeasurementsFairValueHierarchyDomain_74b1c213-872a-4f3a-8e8a-cda92885a315" xlink:to="loc_us-gaap_FairValueInputsLevel1Member_e663a4a7-96d9-425e-a173-45b7ae646e23" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueInputsLevel2Member_15d26e41-2edd-4a3b-9156-47fce388ad12" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FairValueInputsLevel2Member"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FairValueMeasurementsFairValueHierarchyDomain_74b1c213-872a-4f3a-8e8a-cda92885a315" xlink:to="loc_us-gaap_FairValueInputsLevel2Member_15d26e41-2edd-4a3b-9156-47fce388ad12" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueByAssetClassAxis_0e1d4513-0b34-4812-b869-092bebcac7c1" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FairValueByAssetClassAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable_ef66d1bd-6879-4404-ace6-173d85a73610" xlink:to="loc_us-gaap_FairValueByAssetClassAxis_0e1d4513-0b34-4812-b869-092bebcac7c1" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueAssetsMeasuredOnRecurringBasisUnobservableInputReconciliationByAssetClassDomain_0e1d4513-0b34-4812-b869-092bebcac7c1_default" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FairValueAssetsMeasuredOnRecurringBasisUnobservableInputReconciliationByAssetClassDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_FairValueByAssetClassAxis_0e1d4513-0b34-4812-b869-092bebcac7c1" xlink:to="loc_us-gaap_FairValueAssetsMeasuredOnRecurringBasisUnobservableInputReconciliationByAssetClassDomain_0e1d4513-0b34-4812-b869-092bebcac7c1_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueAssetsMeasuredOnRecurringBasisUnobservableInputReconciliationByAssetClassDomain_8dec0707-6dd1-447a-a3f1-66973590120e" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FairValueAssetsMeasuredOnRecurringBasisUnobservableInputReconciliationByAssetClassDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_FairValueByAssetClassAxis_0e1d4513-0b34-4812-b869-092bebcac7c1" xlink:to="loc_us-gaap_FairValueAssetsMeasuredOnRecurringBasisUnobservableInputReconciliationByAssetClassDomain_8dec0707-6dd1-447a-a3f1-66973590120e" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_OtherDerivativesMember_a25c3bc9-a355-439e-a2a6-f099ca7ad311" xlink:href="agnc-20220331.xsd#agnc_OtherDerivativesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FairValueAssetsMeasuredOnRecurringBasisUnobservableInputReconciliationByAssetClassDomain_8dec0707-6dd1-447a-a3f1-66973590120e" xlink:to="loc_agnc_OtherDerivativesMember_a25c3bc9-a355-439e-a2a6-f099ca7ad311" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_InterestRateSwapMember_1ed47965-85d6-4981-b03c-d0f65750901c" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_InterestRateSwapMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FairValueAssetsMeasuredOnRecurringBasisUnobservableInputReconciliationByAssetClassDomain_8dec0707-6dd1-447a-a3f1-66973590120e" xlink:to="loc_us-gaap_InterestRateSwapMember_1ed47965-85d6-4981-b03c-d0f65750901c" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_TBAAndForwardSettlingSecuritiesMember_861fb3e9-3956-4b98-b85d-f14b7b778efe" xlink:href="agnc-20220331.xsd#agnc_TBAAndForwardSettlingSecuritiesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FairValueAssetsMeasuredOnRecurringBasisUnobservableInputReconciliationByAssetClassDomain_8dec0707-6dd1-447a-a3f1-66973590120e" xlink:to="loc_agnc_TBAAndForwardSettlingSecuritiesMember_861fb3e9-3956-4b98-b85d-f14b7b778efe" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FutureMember_a3531ee9-8e93-469a-a875-e7c88b964b76" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FutureMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FairValueAssetsMeasuredOnRecurringBasisUnobservableInputReconciliationByAssetClassDomain_8dec0707-6dd1-447a-a3f1-66973590120e" xlink:to="loc_us-gaap_FutureMember_a3531ee9-8e93-469a-a875-e7c88b964b76" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_SaleOfTBAAndForwardSettlingSecuritiesMember_2d3db72b-f12a-4efa-bd1e-75b870e5bc22" xlink:href="agnc-20220331.xsd#agnc_SaleOfTBAAndForwardSettlingSecuritiesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FairValueAssetsMeasuredOnRecurringBasisUnobservableInputReconciliationByAssetClassDomain_8dec0707-6dd1-447a-a3f1-66973590120e" xlink:to="loc_agnc_SaleOfTBAAndForwardSettlingSecuritiesMember_2d3db72b-f12a-4efa-bd1e-75b870e5bc22" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_USTreasurySecuritiesMember_c53aba08-1fd2-4723-9d2a-e91091e79a9a" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_USTreasurySecuritiesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FairValueAssetsMeasuredOnRecurringBasisUnobservableInputReconciliationByAssetClassDomain_8dec0707-6dd1-447a-a3f1-66973590120e" xlink:to="loc_us-gaap_USTreasurySecuritiesMember_c53aba08-1fd2-4723-9d2a-e91091e79a9a" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueByLiabilityClassAxis_123ba33c-fead-4d39-a520-65cb8bd620a4" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FairValueByLiabilityClassAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable_ef66d1bd-6879-4404-ace6-173d85a73610" xlink:to="loc_us-gaap_FairValueByLiabilityClassAxis_123ba33c-fead-4d39-a520-65cb8bd620a4" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueLiabilitiesMeasuredOnRecurringBasisUnobservableInputReconciliationByLiabilityClassDomain_123ba33c-fead-4d39-a520-65cb8bd620a4_default" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FairValueLiabilitiesMeasuredOnRecurringBasisUnobservableInputReconciliationByLiabilityClassDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_FairValueByLiabilityClassAxis_123ba33c-fead-4d39-a520-65cb8bd620a4" xlink:to="loc_us-gaap_FairValueLiabilitiesMeasuredOnRecurringBasisUnobservableInputReconciliationByLiabilityClassDomain_123ba33c-fead-4d39-a520-65cb8bd620a4_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueLiabilitiesMeasuredOnRecurringBasisUnobservableInputReconciliationByLiabilityClassDomain_5c3759ca-fee3-48f1-9cca-9d369178dc95" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FairValueLiabilitiesMeasuredOnRecurringBasisUnobservableInputReconciliationByLiabilityClassDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_FairValueByLiabilityClassAxis_123ba33c-fead-4d39-a520-65cb8bd620a4" xlink:to="loc_us-gaap_FairValueLiabilitiesMeasuredOnRecurringBasisUnobservableInputReconciliationByLiabilityClassDomain_5c3759ca-fee3-48f1-9cca-9d369178dc95" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_InterestRateSwapMember_37204de0-bb19-41ba-b3d6-371d487dbc3e" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_InterestRateSwapMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FairValueLiabilitiesMeasuredOnRecurringBasisUnobservableInputReconciliationByLiabilityClassDomain_5c3759ca-fee3-48f1-9cca-9d369178dc95" xlink:to="loc_us-gaap_InterestRateSwapMember_37204de0-bb19-41ba-b3d6-371d487dbc3e" xlink:type="arc" order="0"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.agnc.com/role/NetIncomeLossPerCommonShareDetails" xlink:type="simple" xlink:href="agnc-20220331.xsd#NetIncomeLossPerCommonShareDetails"/>
  <link:definitionLink xlink:role="http://www.agnc.com/role/NetIncomeLossPerCommonShareDetails" xlink:type="extended" id="idd416422e05b4243b4e16af7608d7c71_NetIncomeLossPerCommonShareDetails">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EarningsPerShareDilutedLineItems_37f9f6a1-963b-4da8-b960-dd0bded94932" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_EarningsPerShareDilutedLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_WeightedAverageNumberofSharesOutstanding_82b514b0-7e76-465a-ab77-928106187363" xlink:href="agnc-20220331.xsd#agnc_WeightedAverageNumberofSharesOutstanding"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EarningsPerShareDilutedLineItems_37f9f6a1-963b-4da8-b960-dd0bded94932" xlink:to="loc_agnc_WeightedAverageNumberofSharesOutstanding_82b514b0-7e76-465a-ab77-928106187363" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_WeightedAverageNumberofFullyVestedRestrictedStockUnitsandPerformanceShareUnitsOutstanding_3e90fb03-0a79-4ec0-ad33-eab54b947879" xlink:href="agnc-20220331.xsd#agnc_WeightedAverageNumberofFullyVestedRestrictedStockUnitsandPerformanceShareUnitsOutstanding"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EarningsPerShareDilutedLineItems_37f9f6a1-963b-4da8-b960-dd0bded94932" xlink:to="loc_agnc_WeightedAverageNumberofFullyVestedRestrictedStockUnitsandPerformanceShareUnitsOutstanding_3e90fb03-0a79-4ec0-ad33-eab54b947879" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_WeightedAverageNumberOfSharesOutstandingBasic_9990a1cc-2000-41f0-9044-5e7b6ea6b4ca" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_WeightedAverageNumberOfSharesOutstandingBasic"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EarningsPerShareDilutedLineItems_37f9f6a1-963b-4da8-b960-dd0bded94932" xlink:to="loc_us-gaap_WeightedAverageNumberOfSharesOutstandingBasic_9990a1cc-2000-41f0-9044-5e7b6ea6b4ca" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncrementalCommonSharesAttributableToShareBasedPaymentArrangements_b1f952a2-257a-4f03-9840-29d214036f96" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_IncrementalCommonSharesAttributableToShareBasedPaymentArrangements"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EarningsPerShareDilutedLineItems_37f9f6a1-963b-4da8-b960-dd0bded94932" xlink:to="loc_us-gaap_IncrementalCommonSharesAttributableToShareBasedPaymentArrangements_b1f952a2-257a-4f03-9840-29d214036f96" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_WeightedAverageNumberOfDilutedSharesOutstanding_7947ac55-254d-4d9c-9b78-4eb64d22356e" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_WeightedAverageNumberOfDilutedSharesOutstanding"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EarningsPerShareDilutedLineItems_37f9f6a1-963b-4da8-b960-dd0bded94932" xlink:to="loc_us-gaap_WeightedAverageNumberOfDilutedSharesOutstanding_7947ac55-254d-4d9c-9b78-4eb64d22356e" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_NetIncomeLossAvailableToCommonStockholdersBasic_3eed7467-61e5-4080-b5bd-2e11e5c7c4b5" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_NetIncomeLossAvailableToCommonStockholdersBasic"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EarningsPerShareDilutedLineItems_37f9f6a1-963b-4da8-b960-dd0bded94932" xlink:to="loc_us-gaap_NetIncomeLossAvailableToCommonStockholdersBasic_3eed7467-61e5-4080-b5bd-2e11e5c7c4b5" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EarningsPerShareBasic_d2a34833-1d49-4036-9c8e-2ea20fd74353" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_EarningsPerShareBasic"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EarningsPerShareDilutedLineItems_37f9f6a1-963b-4da8-b960-dd0bded94932" xlink:to="loc_us-gaap_EarningsPerShareBasic_d2a34833-1d49-4036-9c8e-2ea20fd74353" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EarningsPerShareDiluted_94bbaae5-c1fa-40a9-8590-4daa5752c57a" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_EarningsPerShareDiluted"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EarningsPerShareDilutedLineItems_37f9f6a1-963b-4da8-b960-dd0bded94932" xlink:to="loc_us-gaap_EarningsPerShareDiluted_94bbaae5-c1fa-40a9-8590-4daa5752c57a" xlink:type="arc" order="7"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EarningsPerShareBasicAndDiluted_4303028f-f408-4426-83ad-3b6ca1828845" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_EarningsPerShareBasicAndDiluted"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EarningsPerShareDilutedLineItems_37f9f6a1-963b-4da8-b960-dd0bded94932" xlink:to="loc_us-gaap_EarningsPerShareBasicAndDiluted_4303028f-f408-4426-83ad-3b6ca1828845" xlink:type="arc" order="8"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareAmount_3cc0c136-2ef4-4498-b77b-4f7c5d699668" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareAmount"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EarningsPerShareDilutedLineItems_37f9f6a1-963b-4da8-b960-dd0bded94932" xlink:to="loc_us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareAmount_3cc0c136-2ef4-4498-b77b-4f7c5d699668" xlink:type="arc" order="9"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfEarningsPerShareDilutedByCommonClassTable_c8ffcbcf-cc4f-4748-acbb-616973757e0c" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ScheduleOfEarningsPerShareDilutedByCommonClassTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_EarningsPerShareDilutedLineItems_37f9f6a1-963b-4da8-b960-dd0bded94932" xlink:to="loc_us-gaap_ScheduleOfEarningsPerShareDilutedByCommonClassTable_c8ffcbcf-cc4f-4748-acbb-616973757e0c" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareByAntidilutiveSecuritiesAxis_62378efa-a852-4b19-99f1-fa0e305d78da" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareByAntidilutiveSecuritiesAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfEarningsPerShareDilutedByCommonClassTable_c8ffcbcf-cc4f-4748-acbb-616973757e0c" xlink:to="loc_us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareByAntidilutiveSecuritiesAxis_62378efa-a852-4b19-99f1-fa0e305d78da" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AntidilutiveSecuritiesNameDomain_62378efa-a852-4b19-99f1-fa0e305d78da_default" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AntidilutiveSecuritiesNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareByAntidilutiveSecuritiesAxis_62378efa-a852-4b19-99f1-fa0e305d78da" xlink:to="loc_us-gaap_AntidilutiveSecuritiesNameDomain_62378efa-a852-4b19-99f1-fa0e305d78da_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AntidilutiveSecuritiesNameDomain_81bcde65-d8f9-44e9-a91f-8347317afed3" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AntidilutiveSecuritiesNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareByAntidilutiveSecuritiesAxis_62378efa-a852-4b19-99f1-fa0e305d78da" xlink:to="loc_us-gaap_AntidilutiveSecuritiesNameDomain_81bcde65-d8f9-44e9-a91f-8347317afed3" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RestrictedStockUnitsRSUMember_c9bbc1d5-4f1d-42ed-995a-c0b8869121ca" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_RestrictedStockUnitsRSUMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AntidilutiveSecuritiesNameDomain_81bcde65-d8f9-44e9-a91f-8347317afed3" xlink:to="loc_us-gaap_RestrictedStockUnitsRSUMember_c9bbc1d5-4f1d-42ed-995a-c0b8869121ca" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StatementClassOfStockAxis_8a774a5a-6a08-4155-b49c-389f9144b643" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_StatementClassOfStockAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfEarningsPerShareDilutedByCommonClassTable_c8ffcbcf-cc4f-4748-acbb-616973757e0c" xlink:to="loc_us-gaap_StatementClassOfStockAxis_8a774a5a-6a08-4155-b49c-389f9144b643" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ClassOfStockDomain_8a774a5a-6a08-4155-b49c-389f9144b643_default" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ClassOfStockDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_StatementClassOfStockAxis_8a774a5a-6a08-4155-b49c-389f9144b643" xlink:to="loc_us-gaap_ClassOfStockDomain_8a774a5a-6a08-4155-b49c-389f9144b643_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ClassOfStockDomain_eb7da57f-58f2-41af-81ee-1dac9075be31" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ClassOfStockDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_StatementClassOfStockAxis_8a774a5a-6a08-4155-b49c-389f9144b643" xlink:to="loc_us-gaap_ClassOfStockDomain_eb7da57f-58f2-41af-81ee-1dac9075be31" xlink:type="arc" order="1"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.agnc.com/role/StockholdersEquityPreferredStockDetails" xlink:type="simple" xlink:href="agnc-20220331.xsd#StockholdersEquityPreferredStockDetails"/>
  <link:definitionLink xlink:role="http://www.agnc.com/role/StockholdersEquityPreferredStockDetails" xlink:type="extended" id="i8c99abad802646a68b1a6d4c28dc9478_StockholdersEquityPreferredStockDetails">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_42f58783-a405-4a71-9893-77888e5a9263" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_PreferredStockBValueIssued_fad11db9-683b-40ff-80b8-374f9a765c3c" xlink:href="agnc-20220331.xsd#agnc_PreferredStockBValueIssued"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_42f58783-a405-4a71-9893-77888e5a9263" xlink:to="loc_agnc_PreferredStockBValueIssued_fad11db9-683b-40ff-80b8-374f9a765c3c" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_PreferredStockBLiquidationPreferenceValue_874b9364-8f6e-47fe-ab3d-fd09f5302433" xlink:href="agnc-20220331.xsd#agnc_PreferredStockBLiquidationPreferenceValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_42f58783-a405-4a71-9893-77888e5a9263" xlink:to="loc_agnc_PreferredStockBLiquidationPreferenceValue_874b9364-8f6e-47fe-ab3d-fd09f5302433" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_PreferredStockPercentInterestPerShare_68acae94-1600-4474-81aa-09ae39c1873e" xlink:href="agnc-20220331.xsd#agnc_PreferredStockPercentInterestPerShare"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_42f58783-a405-4a71-9893-77888e5a9263" xlink:to="loc_agnc_PreferredStockPercentInterestPerShare_68acae94-1600-4474-81aa-09ae39c1873e" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PreferredStockCapitalSharesReservedForFutureIssuance_c01a920f-4945-4710-a6cc-2344f59d9149" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_PreferredStockCapitalSharesReservedForFutureIssuance"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_42f58783-a405-4a71-9893-77888e5a9263" xlink:to="loc_us-gaap_PreferredStockCapitalSharesReservedForFutureIssuance_c01a920f-4945-4710-a6cc-2344f59d9149" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PreferredStockDividendRatePercentage_119b1997-1eac-4572-82b3-072452c5e4cb" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_PreferredStockDividendRatePercentage"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_42f58783-a405-4a71-9893-77888e5a9263" xlink:to="loc_us-gaap_PreferredStockDividendRatePercentage_119b1997-1eac-4572-82b3-072452c5e4cb" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_PreferredStockEValueIssued_895a74ca-7b08-4bc6-812b-133bfe8eb527" xlink:href="agnc-20220331.xsd#agnc_PreferredStockEValueIssued"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_42f58783-a405-4a71-9893-77888e5a9263" xlink:to="loc_agnc_PreferredStockEValueIssued_895a74ca-7b08-4bc6-812b-133bfe8eb527" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_PreferredStockELiquidationPreferenceValue_c345c4f1-c74a-4e08-be37-e5a9ffa951bb" xlink:href="agnc-20220331.xsd#agnc_PreferredStockELiquidationPreferenceValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_42f58783-a405-4a71-9893-77888e5a9263" xlink:to="loc_agnc_PreferredStockELiquidationPreferenceValue_c345c4f1-c74a-4e08-be37-e5a9ffa951bb" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_PreferredStockDividendPaymentRateVariableRateSpread_cf18c865-72cd-4c53-ab6d-8b1f8a75fe64" xlink:href="agnc-20220331.xsd#agnc_PreferredStockDividendPaymentRateVariableRateSpread"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_42f58783-a405-4a71-9893-77888e5a9263" xlink:to="loc_agnc_PreferredStockDividendPaymentRateVariableRateSpread_cf18c865-72cd-4c53-ab6d-8b1f8a75fe64" xlink:type="arc" order="7"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PreferredStockLiquidationPreference_2092302c-5b5b-4ea4-9cde-dfa3bc856f91" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_PreferredStockLiquidationPreference"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_42f58783-a405-4a71-9893-77888e5a9263" xlink:to="loc_us-gaap_PreferredStockLiquidationPreference_2092302c-5b5b-4ea4-9cde-dfa3bc856f91" xlink:type="arc" order="8"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PreferredStockSharesIssued_5ea42e91-87c6-4444-b543-0a42a695c149" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_PreferredStockSharesIssued"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_42f58783-a405-4a71-9893-77888e5a9263" xlink:to="loc_us-gaap_PreferredStockSharesIssued_5ea42e91-87c6-4444-b543-0a42a695c149" xlink:type="arc" order="9"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_PreferredStockFValueIssued_958ca838-dd08-4b70-8632-a4e53c8b22ea" xlink:href="agnc-20220331.xsd#agnc_PreferredStockFValueIssued"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_42f58783-a405-4a71-9893-77888e5a9263" xlink:to="loc_agnc_PreferredStockFValueIssued_958ca838-dd08-4b70-8632-a4e53c8b22ea" xlink:type="arc" order="10"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_PreferredStockDValueIssued_4a5e6b7a-1019-4d0b-a2dc-e47a7dceb49a" xlink:href="agnc-20220331.xsd#agnc_PreferredStockDValueIssued"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_42f58783-a405-4a71-9893-77888e5a9263" xlink:to="loc_agnc_PreferredStockDValueIssued_4a5e6b7a-1019-4d0b-a2dc-e47a7dceb49a" xlink:type="arc" order="11"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_PreferredStockDLiquidationPreferenceValue_1ec10a3b-e7e0-4d11-8247-e485aa510e5b" xlink:href="agnc-20220331.xsd#agnc_PreferredStockDLiquidationPreferenceValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_42f58783-a405-4a71-9893-77888e5a9263" xlink:to="loc_agnc_PreferredStockDLiquidationPreferenceValue_1ec10a3b-e7e0-4d11-8247-e485aa510e5b" xlink:type="arc" order="12"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_PreferredStockAuthorizedButNotIssued_130e3059-72fa-4c3f-9bfc-54040555a643" xlink:href="agnc-20220331.xsd#agnc_PreferredStockAuthorizedButNotIssued"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_42f58783-a405-4a71-9893-77888e5a9263" xlink:to="loc_agnc_PreferredStockAuthorizedButNotIssued_130e3059-72fa-4c3f-9bfc-54040555a643" xlink:type="arc" order="13"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ProceedsFromIssuanceOfRedeemablePreferredStock_189cf398-f8b3-46a7-adc8-4625f77cc6b7" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ProceedsFromIssuanceOfRedeemablePreferredStock"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_42f58783-a405-4a71-9893-77888e5a9263" xlink:to="loc_us-gaap_ProceedsFromIssuanceOfRedeemablePreferredStock_189cf398-f8b3-46a7-adc8-4625f77cc6b7" xlink:type="arc" order="14"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PaymentsForRepurchaseOfRedeemablePreferredStock_ce0029ef-45e0-4fc8-a101-18c413cafdce" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_PaymentsForRepurchaseOfRedeemablePreferredStock"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_42f58783-a405-4a71-9893-77888e5a9263" xlink:to="loc_us-gaap_PaymentsForRepurchaseOfRedeemablePreferredStock_ce0029ef-45e0-4fc8-a101-18c413cafdce" xlink:type="arc" order="15"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_PreferredStockCValueIssued_935d7abe-4176-4a7f-922f-44d34f54e195" xlink:href="agnc-20220331.xsd#agnc_PreferredStockCValueIssued"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_42f58783-a405-4a71-9893-77888e5a9263" xlink:to="loc_agnc_PreferredStockCValueIssued_935d7abe-4176-4a7f-922f-44d34f54e195" xlink:type="arc" order="16"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_PreferredStockCLiquidationPreferenceValue_f1ed22d3-3e5a-4c8b-9757-b9f673e804ff" xlink:href="agnc-20220331.xsd#agnc_PreferredStockCLiquidationPreferenceValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_42f58783-a405-4a71-9893-77888e5a9263" xlink:to="loc_agnc_PreferredStockCLiquidationPreferenceValue_f1ed22d3-3e5a-4c8b-9757-b9f673e804ff" xlink:type="arc" order="17"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PreferredStockValue_6834fd7b-c82b-4f43-bf4f-990b0a73c1f0" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_PreferredStockValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_42f58783-a405-4a71-9893-77888e5a9263" xlink:to="loc_us-gaap_PreferredStockValue_6834fd7b-c82b-4f43-bf4f-990b0a73c1f0" xlink:type="arc" order="18"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PreferredStockLiquidationPreferenceValue_ebf9d9be-6555-498d-9523-903c0142956a" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_PreferredStockLiquidationPreferenceValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_42f58783-a405-4a71-9893-77888e5a9263" xlink:to="loc_us-gaap_PreferredStockLiquidationPreferenceValue_ebf9d9be-6555-498d-9523-903c0142956a" xlink:type="arc" order="19"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_97e2702b-a274-440c-8ad0-a2d46de21eb3" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_42f58783-a405-4a71-9893-77888e5a9263" xlink:to="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_97e2702b-a274-440c-8ad0-a2d46de21eb3" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_VariableRateAxis_bb3eb91c-badf-4ec1-af3e-95c549f71fe0" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_VariableRateAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_97e2702b-a274-440c-8ad0-a2d46de21eb3" xlink:to="loc_us-gaap_VariableRateAxis_bb3eb91c-badf-4ec1-af3e-95c549f71fe0" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_VariableRateDomain_bb3eb91c-badf-4ec1-af3e-95c549f71fe0_default" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_VariableRateDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_VariableRateAxis_bb3eb91c-badf-4ec1-af3e-95c549f71fe0" xlink:to="loc_us-gaap_VariableRateDomain_bb3eb91c-badf-4ec1-af3e-95c549f71fe0_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_VariableRateDomain_59f10a8d-01bb-437d-a8f2-b90a31f3f985" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_VariableRateDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_VariableRateAxis_bb3eb91c-badf-4ec1-af3e-95c549f71fe0" xlink:to="loc_us-gaap_VariableRateDomain_59f10a8d-01bb-437d-a8f2-b90a31f3f985" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PreferredUnitsByNameAxis_3c6c9c76-1168-42e5-8f62-1f252f267fa1" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_PreferredUnitsByNameAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_97e2702b-a274-440c-8ad0-a2d46de21eb3" xlink:to="loc_us-gaap_PreferredUnitsByNameAxis_3c6c9c76-1168-42e5-8f62-1f252f267fa1" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PreferredUnitsClassDomain_3c6c9c76-1168-42e5-8f62-1f252f267fa1_default" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_PreferredUnitsClassDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_PreferredUnitsByNameAxis_3c6c9c76-1168-42e5-8f62-1f252f267fa1" xlink:to="loc_us-gaap_PreferredUnitsClassDomain_3c6c9c76-1168-42e5-8f62-1f252f267fa1_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PreferredUnitsClassDomain_9a9698d9-6b08-45e3-93b8-802039c441a0" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_PreferredUnitsClassDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_PreferredUnitsByNameAxis_3c6c9c76-1168-42e5-8f62-1f252f267fa1" xlink:to="loc_us-gaap_PreferredUnitsClassDomain_9a9698d9-6b08-45e3-93b8-802039c441a0" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_DepositaryShareMember_ce96a562-47b2-4f63-a0d4-b25fb03df1bc" xlink:href="agnc-20220331.xsd#agnc_DepositaryShareMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PreferredUnitsClassDomain_9a9698d9-6b08-45e3-93b8-802039c441a0" xlink:to="loc_agnc_DepositaryShareMember_ce96a562-47b2-4f63-a0d4-b25fb03df1bc" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StatementClassOfStockAxis_0b95ddaa-5c75-40d1-9692-88f8f628e22d" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_StatementClassOfStockAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_97e2702b-a274-440c-8ad0-a2d46de21eb3" xlink:to="loc_us-gaap_StatementClassOfStockAxis_0b95ddaa-5c75-40d1-9692-88f8f628e22d" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ClassOfStockDomain_0b95ddaa-5c75-40d1-9692-88f8f628e22d_default" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ClassOfStockDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_StatementClassOfStockAxis_0b95ddaa-5c75-40d1-9692-88f8f628e22d" xlink:to="loc_us-gaap_ClassOfStockDomain_0b95ddaa-5c75-40d1-9692-88f8f628e22d_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ClassOfStockDomain_b0b80f55-f33b-4781-a09e-a106364a4e3d" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ClassOfStockDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_StatementClassOfStockAxis_0b95ddaa-5c75-40d1-9692-88f8f628e22d" xlink:to="loc_us-gaap_ClassOfStockDomain_b0b80f55-f33b-4781-a09e-a106364a4e3d" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SeriesAPreferredStockMember_196b09c9-8e45-4756-b292-728be039b00a" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_SeriesAPreferredStockMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockDomain_b0b80f55-f33b-4781-a09e-a106364a4e3d" xlink:to="loc_us-gaap_SeriesAPreferredStockMember_196b09c9-8e45-4756-b292-728be039b00a" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SeriesBPreferredStockMember_244b5d29-23c0-4537-bb86-ac9a15f100fa" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_SeriesBPreferredStockMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockDomain_b0b80f55-f33b-4781-a09e-a106364a4e3d" xlink:to="loc_us-gaap_SeriesBPreferredStockMember_244b5d29-23c0-4537-bb86-ac9a15f100fa" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SeriesCPreferredStockMember_807d2fed-6462-4fc1-8fee-136b010f6386" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_SeriesCPreferredStockMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockDomain_b0b80f55-f33b-4781-a09e-a106364a4e3d" xlink:to="loc_us-gaap_SeriesCPreferredStockMember_807d2fed-6462-4fc1-8fee-136b010f6386" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SeriesDPreferredStockMember_c638326c-ebc1-4f20-b670-0bed989b99ee" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_SeriesDPreferredStockMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockDomain_b0b80f55-f33b-4781-a09e-a106364a4e3d" xlink:to="loc_us-gaap_SeriesDPreferredStockMember_c638326c-ebc1-4f20-b670-0bed989b99ee" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SeriesEPreferredStockMember_1a2b2350-30fa-4fc4-9979-9a1daba80926" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_SeriesEPreferredStockMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockDomain_b0b80f55-f33b-4781-a09e-a106364a4e3d" xlink:to="loc_us-gaap_SeriesEPreferredStockMember_1a2b2350-30fa-4fc4-9979-9a1daba80926" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SeriesFPreferredStockMember_d3465b5a-027a-4038-aceb-ae7111fa710e" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_SeriesFPreferredStockMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockDomain_b0b80f55-f33b-4781-a09e-a106364a4e3d" xlink:to="loc_us-gaap_SeriesFPreferredStockMember_d3465b5a-027a-4038-aceb-ae7111fa710e" xlink:type="arc" order="5"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.agnc.com/role/StockholdersEquityCommonStockRepurchaseProgramDetails" xlink:type="simple" xlink:href="agnc-20220331.xsd#StockholdersEquityCommonStockRepurchaseProgramDetails"/>
  <link:definitionLink xlink:role="http://www.agnc.com/role/StockholdersEquityCommonStockRepurchaseProgramDetails" xlink:type="extended" id="i466a07fd60884bc3bc05e1836442f3be_StockholdersEquityCommonStockRepurchaseProgramDetails">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_08f6b250-0f8a-41aa-a7d5-187a704177d6" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockRepurchaseProgramAuthorizedAmount1_302108fb-ea66-4f9f-b1e2-06796b0bad80" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_StockRepurchaseProgramAuthorizedAmount1"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_08f6b250-0f8a-41aa-a7d5-187a704177d6" xlink:to="loc_us-gaap_StockRepurchaseProgramAuthorizedAmount1_302108fb-ea66-4f9f-b1e2-06796b0bad80" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockRepurchasedDuringPeriodShares_425ad9e0-dc37-47fa-a1be-c9d946ae942b" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_StockRepurchasedDuringPeriodShares"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_08f6b250-0f8a-41aa-a7d5-187a704177d6" xlink:to="loc_us-gaap_StockRepurchasedDuringPeriodShares_425ad9e0-dc37-47fa-a1be-c9d946ae942b" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_TreasuryStockAcquiredAverageCostPerShare_00bc09a9-807c-4179-8c31-aeff5d585fb7" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_TreasuryStockAcquiredAverageCostPerShare"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_08f6b250-0f8a-41aa-a7d5-187a704177d6" xlink:to="loc_us-gaap_TreasuryStockAcquiredAverageCostPerShare_00bc09a9-807c-4179-8c31-aeff5d585fb7" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockRepurchasedDuringPeriodValue_ccd9b7d0-9325-402a-93f2-a11d63d78e1d" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_StockRepurchasedDuringPeriodValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_08f6b250-0f8a-41aa-a7d5-187a704177d6" xlink:to="loc_us-gaap_StockRepurchasedDuringPeriodValue_ccd9b7d0-9325-402a-93f2-a11d63d78e1d" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PaymentsForRepurchaseOfCommonStock_8a84985c-4c22-4216-afd9-84fc7bed81ad" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_PaymentsForRepurchaseOfCommonStock"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_08f6b250-0f8a-41aa-a7d5-187a704177d6" xlink:to="loc_us-gaap_PaymentsForRepurchaseOfCommonStock_8a84985c-4c22-4216-afd9-84fc7bed81ad" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_StockRepurchasedDuringPeriodAverageRepurchasePriceindollarspershare_3f1d509e-4ae9-460d-9cdb-8cc36b16ffd0" xlink:href="agnc-20220331.xsd#agnc_StockRepurchasedDuringPeriodAverageRepurchasePriceindollarspershare"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_08f6b250-0f8a-41aa-a7d5-187a704177d6" xlink:to="loc_agnc_StockRepurchasedDuringPeriodAverageRepurchasePriceindollarspershare_3f1d509e-4ae9-460d-9cdb-8cc36b16ffd0" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockRepurchaseProgramRemainingAuthorizedRepurchaseAmount1_01ccd37c-8a06-4e44-bed9-12804d8a69cf" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_StockRepurchaseProgramRemainingAuthorizedRepurchaseAmount1"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_08f6b250-0f8a-41aa-a7d5-187a704177d6" xlink:to="loc_us-gaap_StockRepurchaseProgramRemainingAuthorizedRepurchaseAmount1_01ccd37c-8a06-4e44-bed9-12804d8a69cf" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_StockRepurchasedDuringPeriodTradeDateShares_65fe37bf-0a04-431f-8bcc-a17fbbfe483c" xlink:href="agnc-20220331.xsd#agnc_StockRepurchasedDuringPeriodTradeDateShares"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_08f6b250-0f8a-41aa-a7d5-187a704177d6" xlink:to="loc_agnc_StockRepurchasedDuringPeriodTradeDateShares_65fe37bf-0a04-431f-8bcc-a17fbbfe483c" xlink:type="arc" order="7"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_StockRepurchasedDuringPeriodTradeDateValue_b629ac14-eb1f-4219-81f4-92ea6f9d2e39" xlink:href="agnc-20220331.xsd#agnc_StockRepurchasedDuringPeriodTradeDateValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_08f6b250-0f8a-41aa-a7d5-187a704177d6" xlink:to="loc_agnc_StockRepurchasedDuringPeriodTradeDateValue_b629ac14-eb1f-4219-81f4-92ea6f9d2e39" xlink:type="arc" order="8"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_StockRepurchasedDuringPeriodSettledAfterPeriodValue_737f5696-5a4a-42b6-bd7d-cc5e47a218f1" xlink:href="agnc-20220331.xsd#agnc_StockRepurchasedDuringPeriodSettledAfterPeriodValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_08f6b250-0f8a-41aa-a7d5-187a704177d6" xlink:to="loc_agnc_StockRepurchasedDuringPeriodSettledAfterPeriodValue_737f5696-5a4a-42b6-bd7d-cc5e47a218f1" xlink:type="arc" order="9"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_StockRepurchasedDuringPeriodSettledAfterShares_11fe32a7-fb4e-4f3c-a669-7624915fa3bf" xlink:href="agnc-20220331.xsd#agnc_StockRepurchasedDuringPeriodSettledAfterShares"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_08f6b250-0f8a-41aa-a7d5-187a704177d6" xlink:to="loc_agnc_StockRepurchasedDuringPeriodSettledAfterShares_11fe32a7-fb4e-4f3c-a669-7624915fa3bf" xlink:type="arc" order="10"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_c65a8759-d99c-4445-a9de-af5d85b645d8" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_08f6b250-0f8a-41aa-a7d5-187a704177d6" xlink:to="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_c65a8759-d99c-4445-a9de-af5d85b645d8" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareRepurchaseProgramAxis_2b8a2085-abab-42df-ba4c-0ba8452b6d81" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareRepurchaseProgramAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_c65a8759-d99c-4445-a9de-af5d85b645d8" xlink:to="loc_us-gaap_ShareRepurchaseProgramAxis_2b8a2085-abab-42df-ba4c-0ba8452b6d81" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareRepurchaseProgramDomain_2b8a2085-abab-42df-ba4c-0ba8452b6d81_default" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareRepurchaseProgramDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_ShareRepurchaseProgramAxis_2b8a2085-abab-42df-ba4c-0ba8452b6d81" xlink:to="loc_us-gaap_ShareRepurchaseProgramDomain_2b8a2085-abab-42df-ba4c-0ba8452b6d81_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareRepurchaseProgramDomain_11c64983-cde9-4734-9dd7-1473cc5d2e73" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareRepurchaseProgramDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_ShareRepurchaseProgramAxis_2b8a2085-abab-42df-ba4c-0ba8452b6d81" xlink:to="loc_us-gaap_ShareRepurchaseProgramDomain_11c64983-cde9-4734-9dd7-1473cc5d2e73" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PlanNameDomain_dd90b62a-e329-439c-a8f3-ed8065f8249a" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_PlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_ShareRepurchaseProgramAxis_2b8a2085-abab-42df-ba4c-0ba8452b6d81" xlink:to="loc_us-gaap_PlanNameDomain_dd90b62a-e329-439c-a8f3-ed8065f8249a" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SubsequentEventTypeAxis_5e1f64df-0d7f-42d4-b13f-1e0dcc299ad3" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_SubsequentEventTypeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_c65a8759-d99c-4445-a9de-af5d85b645d8" xlink:to="loc_us-gaap_SubsequentEventTypeAxis_5e1f64df-0d7f-42d4-b13f-1e0dcc299ad3" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SubsequentEventTypeDomain_5e1f64df-0d7f-42d4-b13f-1e0dcc299ad3_default" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_SubsequentEventTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_SubsequentEventTypeAxis_5e1f64df-0d7f-42d4-b13f-1e0dcc299ad3" xlink:to="loc_us-gaap_SubsequentEventTypeDomain_5e1f64df-0d7f-42d4-b13f-1e0dcc299ad3_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SubsequentEventTypeDomain_45f5f9bc-85a1-4f8e-a294-a0cc28fbf607" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_SubsequentEventTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_SubsequentEventTypeAxis_5e1f64df-0d7f-42d4-b13f-1e0dcc299ad3" xlink:to="loc_us-gaap_SubsequentEventTypeDomain_45f5f9bc-85a1-4f8e-a294-a0cc28fbf607" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SubsequentEventMember_da857c9a-18a1-4358-bc0f-4815c78a4932" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_SubsequentEventMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SubsequentEventTypeDomain_45f5f9bc-85a1-4f8e-a294-a0cc28fbf607" xlink:to="loc_us-gaap_SubsequentEventMember_da857c9a-18a1-4358-bc0f-4815c78a4932" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StatementEquityComponentsAxis_4a268fe9-5c02-4c6b-bf8f-469749fd62c7" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_StatementEquityComponentsAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_c65a8759-d99c-4445-a9de-af5d85b645d8" xlink:to="loc_us-gaap_StatementEquityComponentsAxis_4a268fe9-5c02-4c6b-bf8f-469749fd62c7" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EquityComponentDomain_4a268fe9-5c02-4c6b-bf8f-469749fd62c7_default" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_EquityComponentDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_StatementEquityComponentsAxis_4a268fe9-5c02-4c6b-bf8f-469749fd62c7" xlink:to="loc_us-gaap_EquityComponentDomain_4a268fe9-5c02-4c6b-bf8f-469749fd62c7_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EquityComponentDomain_30dcaa18-0b55-4f7b-ab08-a09572d09eea" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_EquityComponentDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_StatementEquityComponentsAxis_4a268fe9-5c02-4c6b-bf8f-469749fd62c7" xlink:to="loc_us-gaap_EquityComponentDomain_30dcaa18-0b55-4f7b-ab08-a09572d09eea" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CommonStockMember_5b86a46a-b3b8-4bd3-9d66-478a2afbed92" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_CommonStockMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EquityComponentDomain_30dcaa18-0b55-4f7b-ab08-a09572d09eea" xlink:to="loc_us-gaap_CommonStockMember_5b86a46a-b3b8-4bd3-9d66-478a2afbed92" xlink:type="arc" order="0"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.agnc.com/role/StockholdersEquityAccumulatedOtherComprehensiveIncomeLossDetails" xlink:type="simple" xlink:href="agnc-20220331.xsd#StockholdersEquityAccumulatedOtherComprehensiveIncomeLossDetails"/>
  <link:definitionLink xlink:role="http://www.agnc.com/role/StockholdersEquityAccumulatedOtherComprehensiveIncomeLossDetails" xlink:type="extended" id="i710c5c4cbc6f45bb902c17a4d2c78c10_StockholdersEquityAccumulatedOtherComprehensiveIncomeLossDetails">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_ad5de249-fac7-4620-9e70-f9814cd0c148" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AccumulatedOtherComprehensiveIncomeLossAvailableForSaleSecuritiesAdjustmentNetOfTax_9beb777b-762f-4137-8abb-f7c4a68d096f" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AccumulatedOtherComprehensiveIncomeLossAvailableForSaleSecuritiesAdjustmentNetOfTax"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_ad5de249-fac7-4620-9e70-f9814cd0c148" xlink:to="loc_us-gaap_AccumulatedOtherComprehensiveIncomeLossAvailableForSaleSecuritiesAdjustmentNetOfTax_9beb777b-762f-4137-8abb-f7c4a68d096f" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DeferredGainLossOnDiscontinuationOfInterestRateFairValueHedge_11f86777-4336-48f3-9125-175c63c07d66" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DeferredGainLossOnDiscontinuationOfInterestRateFairValueHedge"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_ad5de249-fac7-4620-9e70-f9814cd0c148" xlink:to="loc_us-gaap_DeferredGainLossOnDiscontinuationOfInterestRateFairValueHedge_11f86777-4336-48f3-9125-175c63c07d66" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherComprehensiveIncomeUnrealizedHoldingGainLossOnSecuritiesArisingDuringPeriodNetOfTax_a05a95fb-19d9-4f9d-970f-314e113c05bb" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_OtherComprehensiveIncomeUnrealizedHoldingGainLossOnSecuritiesArisingDuringPeriodNetOfTax"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_ad5de249-fac7-4620-9e70-f9814cd0c148" xlink:to="loc_us-gaap_OtherComprehensiveIncomeUnrealizedHoldingGainLossOnSecuritiesArisingDuringPeriodNetOfTax_a05a95fb-19d9-4f9d-970f-314e113c05bb" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_OtherComprehensiveIncomeReclassificationAdjustmentForSaleOfSecurityReversalOfPriorPeriodUnrealizedGainAndLossesOnRealization_ef3c5878-f466-42e3-9e6c-efcb3a120f88" xlink:href="agnc-20220331.xsd#agnc_OtherComprehensiveIncomeReclassificationAdjustmentForSaleOfSecurityReversalOfPriorPeriodUnrealizedGainAndLossesOnRealization"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_ad5de249-fac7-4620-9e70-f9814cd0c148" xlink:to="loc_agnc_OtherComprehensiveIncomeReclassificationAdjustmentForSaleOfSecurityReversalOfPriorPeriodUnrealizedGainAndLossesOnRealization_ef3c5878-f466-42e3-9e6c-efcb3a120f88" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AccumulatedOtherComprehensiveIncomeLossAvailableForSaleSecuritiesAdjustmentNetOfTax_68a73010-a0f0-4c1f-9090-07b1a7230f6c" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AccumulatedOtherComprehensiveIncomeLossAvailableForSaleSecuritiesAdjustmentNetOfTax"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherComprehensiveIncomeUnrealizedGainLossOnDerivativesArisingDuringPeriodNetOfTax_25f75d7d-2081-4409-8d97-f80c9ed0d927" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_OtherComprehensiveIncomeUnrealizedGainLossOnDerivativesArisingDuringPeriodNetOfTax"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_ad5de249-fac7-4620-9e70-f9814cd0c148" xlink:to="loc_us-gaap_OtherComprehensiveIncomeUnrealizedGainLossOnDerivativesArisingDuringPeriodNetOfTax_25f75d7d-2081-4409-8d97-f80c9ed0d927" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_eb6d5d69-8d79-48b8-b067-b4b1a41710b2" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_ad5de249-fac7-4620-9e70-f9814cd0c148" xlink:to="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_eb6d5d69-8d79-48b8-b067-b4b1a41710b2" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DerivativeInstrumentRiskAxis_c1566327-813d-44e6-bdca-0a4b46db888d" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DerivativeInstrumentRiskAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_eb6d5d69-8d79-48b8-b067-b4b1a41710b2" xlink:to="loc_us-gaap_DerivativeInstrumentRiskAxis_c1566327-813d-44e6-bdca-0a4b46db888d" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DerivativeContractTypeDomain_c1566327-813d-44e6-bdca-0a4b46db888d_default" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DerivativeContractTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_DerivativeInstrumentRiskAxis_c1566327-813d-44e6-bdca-0a4b46db888d" xlink:to="loc_us-gaap_DerivativeContractTypeDomain_c1566327-813d-44e6-bdca-0a4b46db888d_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DerivativeContractTypeDomain_2fe86eb1-2032-42c7-8a96-5689efdb5227" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DerivativeContractTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_DerivativeInstrumentRiskAxis_c1566327-813d-44e6-bdca-0a4b46db888d" xlink:to="loc_us-gaap_DerivativeContractTypeDomain_2fe86eb1-2032-42c7-8a96-5689efdb5227" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_InterestRateSwapMember_19fb3d9d-8295-4bfa-ab01-f33605b13e00" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_InterestRateSwapMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DerivativeContractTypeDomain_2fe86eb1-2032-42c7-8a96-5689efdb5227" xlink:to="loc_us-gaap_InterestRateSwapMember_19fb3d9d-8295-4bfa-ab01-f33605b13e00" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AdjustmentsForChangeInAccountingPrincipleAxis_f48a6a48-514f-476c-8210-ec3809b406f7" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AdjustmentsForChangeInAccountingPrincipleAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_eb6d5d69-8d79-48b8-b067-b4b1a41710b2" xlink:to="loc_us-gaap_AdjustmentsForChangeInAccountingPrincipleAxis_f48a6a48-514f-476c-8210-ec3809b406f7" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ChangeInAccountingPrincipleMember_f48a6a48-514f-476c-8210-ec3809b406f7_default" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ChangeInAccountingPrincipleMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_AdjustmentsForChangeInAccountingPrincipleAxis_f48a6a48-514f-476c-8210-ec3809b406f7" xlink:to="loc_us-gaap_ChangeInAccountingPrincipleMember_f48a6a48-514f-476c-8210-ec3809b406f7_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ChangeInAccountingPrincipleMember_87653c96-ee78-4b02-b3f0-09f80ba9c30f" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ChangeInAccountingPrincipleMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_AdjustmentsForChangeInAccountingPrincipleAxis_f48a6a48-514f-476c-8210-ec3809b406f7" xlink:to="loc_us-gaap_ChangeInAccountingPrincipleMember_87653c96-ee78-4b02-b3f0-09f80ba9c30f" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_DiscontinuationOfElectionToAccountForInterestRateSwapsAsDesignatedCashFlowHedgesMember_d4c4290f-4762-45c3-ab23-988ef714dda6" xlink:href="agnc-20220331.xsd#agnc_DiscontinuationOfElectionToAccountForInterestRateSwapsAsDesignatedCashFlowHedgesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ChangeInAccountingPrincipleMember_87653c96-ee78-4b02-b3f0-09f80ba9c30f" xlink:to="loc_agnc_DiscontinuationOfElectionToAccountForInterestRateSwapsAsDesignatedCashFlowHedgesMember_d4c4290f-4762-45c3-ab23-988ef714dda6" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FinancialInstrumentAxis_84e2350a-71fb-4f37-b3d6-893ceefff331" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FinancialInstrumentAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_eb6d5d69-8d79-48b8-b067-b4b1a41710b2" xlink:to="loc_us-gaap_FinancialInstrumentAxis_84e2350a-71fb-4f37-b3d6-893ceefff331" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_84e2350a-71fb-4f37-b3d6-893ceefff331_default" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_FinancialInstrumentAxis_84e2350a-71fb-4f37-b3d6-893ceefff331" xlink:to="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_84e2350a-71fb-4f37-b3d6-893ceefff331_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_014f2385-bf37-4741-a102-0cf1ffe4bfaf" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_FinancialInstrumentAxis_84e2350a-71fb-4f37-b3d6-893ceefff331" xlink:to="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_014f2385-bf37-4741-a102-0cf1ffe4bfaf" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AgencySecuritiesMember_b05f76b3-9ae2-485f-9503-4d65330bfc97" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AgencySecuritiesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_014f2385-bf37-4741-a102-0cf1ffe4bfaf" xlink:to="loc_us-gaap_AgencySecuritiesMember_b05f76b3-9ae2-485f-9503-4d65330bfc97" xlink:type="arc" order="0"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.agnc.com/role/StockholdersEquityFollowOnEquityOfferingsDetails" xlink:type="simple" xlink:href="agnc-20220331.xsd#StockholdersEquityFollowOnEquityOfferingsDetails"/>
  <link:definitionLink xlink:role="http://www.agnc.com/role/StockholdersEquityFollowOnEquityOfferingsDetails" xlink:type="extended" id="idadfb1f38a8d46eca27566e442cb3b51_StockholdersEquityFollowOnEquityOfferingsDetails">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ClassOfStockLineItems_c41d30a9-1b0b-449d-93c6-a890d047f47e" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ClassOfStockLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SaleOfStockPricePerShare_b601f552-14b8-48f4-bb29-c2ba7a6a8416" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_SaleOfStockPricePerShare"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockLineItems_c41d30a9-1b0b-449d-93c6-a890d047f47e" xlink:to="loc_us-gaap_SaleOfStockPricePerShare_b601f552-14b8-48f4-bb29-c2ba7a6a8416" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockIssuedDuringPeriodSharesNewIssues_9566c385-9f9b-43c4-bea3-d312c0181b79" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_StockIssuedDuringPeriodSharesNewIssues"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockLineItems_c41d30a9-1b0b-449d-93c6-a890d047f47e" xlink:to="loc_us-gaap_StockIssuedDuringPeriodSharesNewIssues_9566c385-9f9b-43c4-bea3-d312c0181b79" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockIssuedDuringPeriodValueNewIssues_0dc61eda-123c-4201-bce8-aed2a7800d1c" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_StockIssuedDuringPeriodValueNewIssues"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockLineItems_c41d30a9-1b0b-449d-93c6-a890d047f47e" xlink:to="loc_us-gaap_StockIssuedDuringPeriodValueNewIssues_0dc61eda-123c-4201-bce8-aed2a7800d1c" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfStockByClassTable_d292dcfc-7666-4df3-a08f-d1e2da9b044c" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ScheduleOfStockByClassTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_ClassOfStockLineItems_c41d30a9-1b0b-449d-93c6-a890d047f47e" xlink:to="loc_us-gaap_ScheduleOfStockByClassTable_d292dcfc-7666-4df3-a08f-d1e2da9b044c" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SubsidiarySaleOfStockAxis_2b3a8e02-0435-41b8-a87e-1b16ebd36a6d" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_SubsidiarySaleOfStockAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfStockByClassTable_d292dcfc-7666-4df3-a08f-d1e2da9b044c" xlink:to="loc_us-gaap_SubsidiarySaleOfStockAxis_2b3a8e02-0435-41b8-a87e-1b16ebd36a6d" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SaleOfStockNameOfTransactionDomain_2b3a8e02-0435-41b8-a87e-1b16ebd36a6d_default" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_SaleOfStockNameOfTransactionDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_SubsidiarySaleOfStockAxis_2b3a8e02-0435-41b8-a87e-1b16ebd36a6d" xlink:to="loc_us-gaap_SaleOfStockNameOfTransactionDomain_2b3a8e02-0435-41b8-a87e-1b16ebd36a6d_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SaleOfStockNameOfTransactionDomain_c178945a-0457-4f15-bb1b-070e9d6cd584" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_SaleOfStockNameOfTransactionDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_SubsidiarySaleOfStockAxis_2b3a8e02-0435-41b8-a87e-1b16ebd36a6d" xlink:to="loc_us-gaap_SaleOfStockNameOfTransactionDomain_c178945a-0457-4f15-bb1b-070e9d6cd584" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_FollowOnPublicOfferingMember_247e8860-a1c6-4474-874b-841155ac019f" xlink:href="agnc-20220331.xsd#agnc_FollowOnPublicOfferingMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SaleOfStockNameOfTransactionDomain_c178945a-0457-4f15-bb1b-070e9d6cd584" xlink:to="loc_agnc_FollowOnPublicOfferingMember_247e8860-a1c6-4474-874b-841155ac019f" xlink:type="arc" order="0"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.agnc.com/role/StockholdersEquityAttheMarketOfferingProgramDetails" xlink:type="simple" xlink:href="agnc-20220331.xsd#StockholdersEquityAttheMarketOfferingProgramDetails"/>
  <link:definitionLink xlink:role="http://www.agnc.com/role/StockholdersEquityAttheMarketOfferingProgramDetails" xlink:type="extended" id="i2f94fc0c7f4b4641ad8423bbe6cfe3b0_StockholdersEquityAttheMarketOfferingProgramDetails">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_f236919b-5c5e-4b00-ad62-9545d3c552ef" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_CommonstockValueofSharesApprovedforFutureIssuance_9f930331-795b-44cd-b183-d6e0e790b088" xlink:href="agnc-20220331.xsd#agnc_CommonstockValueofSharesApprovedforFutureIssuance"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_f236919b-5c5e-4b00-ad62-9545d3c552ef" xlink:to="loc_agnc_CommonstockValueofSharesApprovedforFutureIssuance_9f930331-795b-44cd-b183-d6e0e790b088" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_CommonstockValueofSharesRemainingforFutureIssuance_cdf11f0b-f9f9-4d8b-9d3d-17356e67e3dc" xlink:href="agnc-20220331.xsd#agnc_CommonstockValueofSharesRemainingforFutureIssuance"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_f236919b-5c5e-4b00-ad62-9545d3c552ef" xlink:to="loc_agnc_CommonstockValueofSharesRemainingforFutureIssuance_cdf11f0b-f9f9-4d8b-9d3d-17356e67e3dc" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockIssuedDuringPeriodSharesNewIssues_b63237a9-daa3-4b80-a70e-e1bc7a1bf91e" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_StockIssuedDuringPeriodSharesNewIssues"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_f236919b-5c5e-4b00-ad62-9545d3c552ef" xlink:to="loc_us-gaap_StockIssuedDuringPeriodSharesNewIssues_b63237a9-daa3-4b80-a70e-e1bc7a1bf91e" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockIssuedDuringPeriodValueNewIssues_dbbd86fa-8972-427f-83f5-c0f072050ec0" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_StockIssuedDuringPeriodValueNewIssues"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_f236919b-5c5e-4b00-ad62-9545d3c552ef" xlink:to="loc_us-gaap_StockIssuedDuringPeriodValueNewIssues_dbbd86fa-8972-427f-83f5-c0f072050ec0" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SaleOfStockPricePerShare_ecd4fbeb-56a6-42c2-9c60-996923365d54" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_SaleOfStockPricePerShare"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_f236919b-5c5e-4b00-ad62-9545d3c552ef" xlink:to="loc_us-gaap_SaleOfStockPricePerShare_ecd4fbeb-56a6-42c2-9c60-996923365d54" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_f2979cfb-0e1a-4d04-953c-f8f17086a07e" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_f236919b-5c5e-4b00-ad62-9545d3c552ef" xlink:to="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_f2979cfb-0e1a-4d04-953c-f8f17086a07e" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SubsidiarySaleOfStockAxis_9b0714ff-1a10-4fdf-8827-6de580084826" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_SubsidiarySaleOfStockAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_f2979cfb-0e1a-4d04-953c-f8f17086a07e" xlink:to="loc_us-gaap_SubsidiarySaleOfStockAxis_9b0714ff-1a10-4fdf-8827-6de580084826" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SaleOfStockNameOfTransactionDomain_9b0714ff-1a10-4fdf-8827-6de580084826_default" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_SaleOfStockNameOfTransactionDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_SubsidiarySaleOfStockAxis_9b0714ff-1a10-4fdf-8827-6de580084826" xlink:to="loc_us-gaap_SaleOfStockNameOfTransactionDomain_9b0714ff-1a10-4fdf-8827-6de580084826_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SaleOfStockNameOfTransactionDomain_3e3a91d1-4b9c-4f5b-8f9e-db48dcddb556" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_SaleOfStockNameOfTransactionDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_SubsidiarySaleOfStockAxis_9b0714ff-1a10-4fdf-8827-6de580084826" xlink:to="loc_us-gaap_SaleOfStockNameOfTransactionDomain_3e3a91d1-4b9c-4f5b-8f9e-db48dcddb556" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_CommonStockAtTheMarketSaleAgreementMember_0c79c02e-3b3b-44d9-b92c-e97a1f0d2235" xlink:href="agnc-20220331.xsd#agnc_CommonStockAtTheMarketSaleAgreementMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SaleOfStockNameOfTransactionDomain_3e3a91d1-4b9c-4f5b-8f9e-db48dcddb556" xlink:to="loc_agnc_CommonStockAtTheMarketSaleAgreementMember_0c79c02e-3b3b-44d9-b92c-e97a1f0d2235" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StatementClassOfStockAxis_c18d3b88-8ec8-43de-84a4-e2a11f68d1e6" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_StatementClassOfStockAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_f2979cfb-0e1a-4d04-953c-f8f17086a07e" xlink:to="loc_us-gaap_StatementClassOfStockAxis_c18d3b88-8ec8-43de-84a4-e2a11f68d1e6" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ClassOfStockDomain_c18d3b88-8ec8-43de-84a4-e2a11f68d1e6_default" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ClassOfStockDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_StatementClassOfStockAxis_c18d3b88-8ec8-43de-84a4-e2a11f68d1e6" xlink:to="loc_us-gaap_ClassOfStockDomain_c18d3b88-8ec8-43de-84a4-e2a11f68d1e6_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ClassOfStockDomain_17a6dcd3-8960-4446-a543-f4460897b1b3" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ClassOfStockDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_StatementClassOfStockAxis_c18d3b88-8ec8-43de-84a4-e2a11f68d1e6" xlink:to="loc_us-gaap_ClassOfStockDomain_17a6dcd3-8960-4446-a543-f4460897b1b3" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SeriesAPreferredStockMember_21e5dacb-0cfd-4d42-8d4f-d3387774c4fc" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_SeriesAPreferredStockMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockDomain_17a6dcd3-8960-4446-a543-f4460897b1b3" xlink:to="loc_us-gaap_SeriesAPreferredStockMember_21e5dacb-0cfd-4d42-8d4f-d3387774c4fc" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StatementEquityComponentsAxis_03459910-6dbc-4c49-a0a3-65ff9f6a26d0" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_StatementEquityComponentsAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_f2979cfb-0e1a-4d04-953c-f8f17086a07e" xlink:to="loc_us-gaap_StatementEquityComponentsAxis_03459910-6dbc-4c49-a0a3-65ff9f6a26d0" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EquityComponentDomain_03459910-6dbc-4c49-a0a3-65ff9f6a26d0_default" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_EquityComponentDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_StatementEquityComponentsAxis_03459910-6dbc-4c49-a0a3-65ff9f6a26d0" xlink:to="loc_us-gaap_EquityComponentDomain_03459910-6dbc-4c49-a0a3-65ff9f6a26d0_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EquityComponentDomain_1b7ac3f7-a27a-4c9e-8413-55986a714189" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_EquityComponentDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_StatementEquityComponentsAxis_03459910-6dbc-4c49-a0a3-65ff9f6a26d0" xlink:to="loc_us-gaap_EquityComponentDomain_1b7ac3f7-a27a-4c9e-8413-55986a714189" xlink:type="arc" order="1"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.agnc.com/role/StockholdersEquityDividendReinvestmentandDirectStockPurchasePlanDetails" xlink:type="simple" xlink:href="agnc-20220331.xsd#StockholdersEquityDividendReinvestmentandDirectStockPurchasePlanDetails"/>
  <link:definitionLink xlink:role="http://www.agnc.com/role/StockholdersEquityDividendReinvestmentandDirectStockPurchasePlanDetails" xlink:type="extended" id="icb62fb873312455fa3c4fdbd40bb0650_StockholdersEquityDividendReinvestmentandDirectStockPurchasePlanDetails">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_57b84c3b-6e02-4418-adac-6161a11a69d5" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DividendsPreferredStock_489c5851-a9bd-4a50-b50b-54870a45a64c" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DividendsPreferredStock"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_57b84c3b-6e02-4418-adac-6161a11a69d5" xlink:to="loc_us-gaap_DividendsPreferredStock_489c5851-a9bd-4a50-b50b-54870a45a64c" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PreferredStockDividendRatePerDollarAmount_82b25655-c522-49c9-a103-e94316ce24eb" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_PreferredStockDividendRatePerDollarAmount"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_57b84c3b-6e02-4418-adac-6161a11a69d5" xlink:to="loc_us-gaap_PreferredStockDividendRatePerDollarAmount_82b25655-c522-49c9-a103-e94316ce24eb" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DividendsCommonStock_d1dd9094-b811-4fc2-91f9-d0c265dd81fd" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DividendsCommonStock"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_57b84c3b-6e02-4418-adac-6161a11a69d5" xlink:to="loc_us-gaap_DividendsCommonStock_d1dd9094-b811-4fc2-91f9-d0c265dd81fd" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CommonStockDividendsPerShareCashPaid_052b70d6-ae3a-4ebf-a23d-b521ca6886a2" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_CommonStockDividendsPerShareCashPaid"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_57b84c3b-6e02-4418-adac-6161a11a69d5" xlink:to="loc_us-gaap_CommonStockDividendsPerShareCashPaid_052b70d6-ae3a-4ebf-a23d-b521ca6886a2" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_a647f4a9-405b-4bce-af8b-214326dcaa6c" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_57b84c3b-6e02-4418-adac-6161a11a69d5" xlink:to="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_a647f4a9-405b-4bce-af8b-214326dcaa6c" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StatementClassOfStockAxis_60e2a0a6-59a0-4f51-bcd6-68da14341179" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_StatementClassOfStockAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_a647f4a9-405b-4bce-af8b-214326dcaa6c" xlink:to="loc_us-gaap_StatementClassOfStockAxis_60e2a0a6-59a0-4f51-bcd6-68da14341179" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ClassOfStockDomain_60e2a0a6-59a0-4f51-bcd6-68da14341179_default" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ClassOfStockDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_StatementClassOfStockAxis_60e2a0a6-59a0-4f51-bcd6-68da14341179" xlink:to="loc_us-gaap_ClassOfStockDomain_60e2a0a6-59a0-4f51-bcd6-68da14341179_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ClassOfStockDomain_99e40820-930b-4245-89c6-9474308101a0" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ClassOfStockDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_StatementClassOfStockAxis_60e2a0a6-59a0-4f51-bcd6-68da14341179" xlink:to="loc_us-gaap_ClassOfStockDomain_99e40820-930b-4245-89c6-9474308101a0" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PreferredClassBMember_f4383b8d-e50e-4a0c-9db0-2567683dda17" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_PreferredClassBMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockDomain_99e40820-930b-4245-89c6-9474308101a0" xlink:to="loc_us-gaap_PreferredClassBMember_f4383b8d-e50e-4a0c-9db0-2567683dda17" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SeriesCPreferredStockMember_dd9cf0eb-536f-4a34-810f-e7d10d6c1eec" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_SeriesCPreferredStockMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockDomain_99e40820-930b-4245-89c6-9474308101a0" xlink:to="loc_us-gaap_SeriesCPreferredStockMember_dd9cf0eb-536f-4a34-810f-e7d10d6c1eec" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SeriesDPreferredStockMember_b6a38a1e-3bbc-42eb-914a-9d4bded73600" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_SeriesDPreferredStockMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockDomain_99e40820-930b-4245-89c6-9474308101a0" xlink:to="loc_us-gaap_SeriesDPreferredStockMember_b6a38a1e-3bbc-42eb-914a-9d4bded73600" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SeriesEPreferredStockMember_ef77e29f-0289-4be9-a2ca-21f96397b547" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_SeriesEPreferredStockMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockDomain_99e40820-930b-4245-89c6-9474308101a0" xlink:to="loc_us-gaap_SeriesEPreferredStockMember_ef77e29f-0289-4be9-a2ca-21f96397b547" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StatementEquityComponentsAxis_4715f700-591a-40c3-9043-fc789f895fb3" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_StatementEquityComponentsAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_a647f4a9-405b-4bce-af8b-214326dcaa6c" xlink:to="loc_us-gaap_StatementEquityComponentsAxis_4715f700-591a-40c3-9043-fc789f895fb3" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EquityComponentDomain_4715f700-591a-40c3-9043-fc789f895fb3_default" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_EquityComponentDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_StatementEquityComponentsAxis_4715f700-591a-40c3-9043-fc789f895fb3" xlink:to="loc_us-gaap_EquityComponentDomain_4715f700-591a-40c3-9043-fc789f895fb3_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EquityComponentDomain_608b5c63-e796-46ca-aa1d-59af65ea7248" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_EquityComponentDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_StatementEquityComponentsAxis_4715f700-591a-40c3-9043-fc789f895fb3" xlink:to="loc_us-gaap_EquityComponentDomain_608b5c63-e796-46ca-aa1d-59af65ea7248" xlink:type="arc" order="1"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.agnc.com/role/StockholdersEquityLongtermIncentivePlanDetails" xlink:type="simple" xlink:href="agnc-20220331.xsd#StockholdersEquityLongtermIncentivePlanDetails"/>
  <link:definitionLink xlink:role="http://www.agnc.com/role/StockholdersEquityLongtermIncentivePlanDetails" xlink:type="extended" id="if46fdc846f55485e8bb3829e92e1147c_StockholdersEquityLongtermIncentivePlanDetails">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_09d59257-7593-4195-b586-3577d20630a8" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_6d5dc523-9606-42a3-a0ad-9bf24953caac" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_09d59257-7593-4195-b586-3577d20630a8" xlink:to="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_6d5dc523-9606-42a3-a0ad-9bf24953caac" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_TitleOfIndividualAxis_bf436634-cc5c-492f-b98c-9ff3ff26d5c2" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_TitleOfIndividualAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_6d5dc523-9606-42a3-a0ad-9bf24953caac" xlink:to="loc_srt_TitleOfIndividualAxis_bf436634-cc5c-492f-b98c-9ff3ff26d5c2" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_TitleOfIndividualWithRelationshipToEntityDomain_bf436634-cc5c-492f-b98c-9ff3ff26d5c2_default" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_TitleOfIndividualWithRelationshipToEntityDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_TitleOfIndividualAxis_bf436634-cc5c-492f-b98c-9ff3ff26d5c2" xlink:to="loc_srt_TitleOfIndividualWithRelationshipToEntityDomain_bf436634-cc5c-492f-b98c-9ff3ff26d5c2_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_TitleOfIndividualWithRelationshipToEntityDomain_75d56bf5-4285-4aaa-bcb9-53348ec40b0c" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_TitleOfIndividualWithRelationshipToEntityDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_TitleOfIndividualAxis_bf436634-cc5c-492f-b98c-9ff3ff26d5c2" xlink:to="loc_srt_TitleOfIndividualWithRelationshipToEntityDomain_75d56bf5-4285-4aaa-bcb9-53348ec40b0c" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RelatedPartyTransactionsByRelatedPartyAxis_1954229f-6f1c-4197-a3e1-a6d28946587f" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_RelatedPartyTransactionsByRelatedPartyAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_6d5dc523-9606-42a3-a0ad-9bf24953caac" xlink:to="loc_us-gaap_RelatedPartyTransactionsByRelatedPartyAxis_1954229f-6f1c-4197-a3e1-a6d28946587f" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RelatedPartyDomain_1954229f-6f1c-4197-a3e1-a6d28946587f_default" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_RelatedPartyDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_RelatedPartyTransactionsByRelatedPartyAxis_1954229f-6f1c-4197-a3e1-a6d28946587f" xlink:to="loc_us-gaap_RelatedPartyDomain_1954229f-6f1c-4197-a3e1-a6d28946587f_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RelatedPartyDomain_832584bb-04a6-4d1e-9d5e-be3a7f9b40d6" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_RelatedPartyDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_RelatedPartyTransactionsByRelatedPartyAxis_1954229f-6f1c-4197-a3e1-a6d28946587f" xlink:to="loc_us-gaap_RelatedPartyDomain_832584bb-04a6-4d1e-9d5e-be3a7f9b40d6" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AwardTypeAxis_c7ffc754-bddb-42bd-a2ca-e371b25cc136" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AwardTypeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_6d5dc523-9606-42a3-a0ad-9bf24953caac" xlink:to="loc_us-gaap_AwardTypeAxis_c7ffc754-bddb-42bd-a2ca-e371b25cc136" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_c7ffc754-bddb-42bd-a2ca-e371b25cc136_default" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_AwardTypeAxis_c7ffc754-bddb-42bd-a2ca-e371b25cc136" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_c7ffc754-bddb-42bd-a2ca-e371b25cc136_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_02e08cc0-217c-4f61-aa6b-026ecefa7810" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_AwardTypeAxis_c7ffc754-bddb-42bd-a2ca-e371b25cc136" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_02e08cc0-217c-4f61-aa6b-026ecefa7810" xlink:type="arc" order="1"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.agnc.com/role/StockholdersEquityScheduleofDividendsDeclaredDetails" xlink:type="simple" xlink:href="agnc-20220331.xsd#StockholdersEquityScheduleofDividendsDeclaredDetails"/>
  <link:definitionLink xlink:role="http://www.agnc.com/role/StockholdersEquityScheduleofDividendsDeclaredDetails" xlink:type="extended" id="i090a545693354f66a950ff7a8c1291e9_StockholdersEquityScheduleofDividendsDeclaredDetails">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_b318053e-40e6-4025-9463-f5d8f6aa5f2b" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DividendsPreferredStock_05c984bd-ebd6-483c-9cf5-cbbbafcb7c1f" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DividendsPreferredStock"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_b318053e-40e6-4025-9463-f5d8f6aa5f2b" xlink:to="loc_us-gaap_DividendsPreferredStock_05c984bd-ebd6-483c-9cf5-cbbbafcb7c1f" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PreferredStockDividendsPerShareDeclared_fc74ae95-6a86-4971-8139-3f540589a135" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_PreferredStockDividendsPerShareDeclared"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_b318053e-40e6-4025-9463-f5d8f6aa5f2b" xlink:to="loc_us-gaap_PreferredStockDividendsPerShareDeclared_fc74ae95-6a86-4971-8139-3f540589a135" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DividendsCommonStock_3583a755-1b02-4e86-bf0c-dcf1b35a61b8" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DividendsCommonStock"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_b318053e-40e6-4025-9463-f5d8f6aa5f2b" xlink:to="loc_us-gaap_DividendsCommonStock_3583a755-1b02-4e86-bf0c-dcf1b35a61b8" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CommonStockDividendsPerShareDeclared_996bc4c1-7462-4081-8d34-ece81c5d9667" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_CommonStockDividendsPerShareDeclared"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_b318053e-40e6-4025-9463-f5d8f6aa5f2b" xlink:to="loc_us-gaap_CommonStockDividendsPerShareDeclared_996bc4c1-7462-4081-8d34-ece81c5d9667" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PreferredStockDividendsPerShareCashPaid_5bb999bc-bbec-45b4-b7ab-d6bf65ad212e" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_PreferredStockDividendsPerShareCashPaid"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_b318053e-40e6-4025-9463-f5d8f6aa5f2b" xlink:to="loc_us-gaap_PreferredStockDividendsPerShareCashPaid_5bb999bc-bbec-45b4-b7ab-d6bf65ad212e" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CommonStockDividendsPerShareCashPaid_0cdb96d2-b90d-4590-8734-b6decf20ecb4" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_CommonStockDividendsPerShareCashPaid"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_b318053e-40e6-4025-9463-f5d8f6aa5f2b" xlink:to="loc_us-gaap_CommonStockDividendsPerShareCashPaid_0cdb96d2-b90d-4590-8734-b6decf20ecb4" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_OrdinaryDividendsPerShare_ddd608af-6539-4d63-9237-24ffc8a91668" xlink:href="agnc-20220331.xsd#agnc_OrdinaryDividendsPerShare"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_b318053e-40e6-4025-9463-f5d8f6aa5f2b" xlink:to="loc_agnc_OrdinaryDividendsPerShare_ddd608af-6539-4d63-9237-24ffc8a91668" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_LongTermCapitalGainDividendPerShare_6879ff10-cf70-4885-b631-1d4e2959a98a" xlink:href="agnc-20220331.xsd#agnc_LongTermCapitalGainDividendPerShare"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_b318053e-40e6-4025-9463-f5d8f6aa5f2b" xlink:to="loc_agnc_LongTermCapitalGainDividendPerShare_6879ff10-cf70-4885-b631-1d4e2959a98a" xlink:type="arc" order="7"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_NonDividendDistributionsPerShare_d55cca5e-e387-4583-a00a-2fb10b44cbcc" xlink:href="agnc-20220331.xsd#agnc_NonDividendDistributionsPerShare"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_b318053e-40e6-4025-9463-f5d8f6aa5f2b" xlink:to="loc_agnc_NonDividendDistributionsPerShare_d55cca5e-e387-4583-a00a-2fb10b44cbcc" xlink:type="arc" order="8"/>
    <link:loc xlink:type="locator" xlink:label="loc_agnc_Section199ADividendsPerShare_5a0fa362-fa1a-4b3e-8bbc-e5ca72c8f38b" xlink:href="agnc-20220331.xsd#agnc_Section199ADividendsPerShare"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_b318053e-40e6-4025-9463-f5d8f6aa5f2b" xlink:to="loc_agnc_Section199ADividendsPerShare_5a0fa362-fa1a-4b3e-8bbc-e5ca72c8f38b" xlink:type="arc" order="9"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_843292e7-2103-4249-9756-17a88dd68cde" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_b318053e-40e6-4025-9463-f5d8f6aa5f2b" xlink:to="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_843292e7-2103-4249-9756-17a88dd68cde" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StatementClassOfStockAxis_37f30d9c-a9c5-47c4-a18e-81862a425718" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_StatementClassOfStockAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_843292e7-2103-4249-9756-17a88dd68cde" xlink:to="loc_us-gaap_StatementClassOfStockAxis_37f30d9c-a9c5-47c4-a18e-81862a425718" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ClassOfStockDomain_37f30d9c-a9c5-47c4-a18e-81862a425718_default" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ClassOfStockDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_StatementClassOfStockAxis_37f30d9c-a9c5-47c4-a18e-81862a425718" xlink:to="loc_us-gaap_ClassOfStockDomain_37f30d9c-a9c5-47c4-a18e-81862a425718_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ClassOfStockDomain_340bd7d4-af7d-4032-8ba9-991e246c3ded" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ClassOfStockDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_StatementClassOfStockAxis_37f30d9c-a9c5-47c4-a18e-81862a425718" xlink:to="loc_us-gaap_ClassOfStockDomain_340bd7d4-af7d-4032-8ba9-991e246c3ded" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PreferredClassBMember_064c4329-68d3-45b7-ae47-693cbbc1ce79" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_PreferredClassBMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockDomain_340bd7d4-af7d-4032-8ba9-991e246c3ded" xlink:to="loc_us-gaap_PreferredClassBMember_064c4329-68d3-45b7-ae47-693cbbc1ce79" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SeriesCPreferredStockMember_c6531449-5e44-4255-b604-26b33e97fabe" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_SeriesCPreferredStockMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockDomain_340bd7d4-af7d-4032-8ba9-991e246c3ded" xlink:to="loc_us-gaap_SeriesCPreferredStockMember_c6531449-5e44-4255-b604-26b33e97fabe" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SeriesDPreferredStockMember_ce9f01cf-6fdc-4771-af58-ebfa8f06c778" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_SeriesDPreferredStockMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockDomain_340bd7d4-af7d-4032-8ba9-991e246c3ded" xlink:to="loc_us-gaap_SeriesDPreferredStockMember_ce9f01cf-6fdc-4771-af58-ebfa8f06c778" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SeriesEPreferredStockMember_515435c8-182c-499f-aa47-dfba67409317" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_SeriesEPreferredStockMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockDomain_340bd7d4-af7d-4032-8ba9-991e246c3ded" xlink:to="loc_us-gaap_SeriesEPreferredStockMember_515435c8-182c-499f-aa47-dfba67409317" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SeriesFPreferredStockMember_ef172e89-abe1-4f22-afd7-efcd2073257f" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_SeriesFPreferredStockMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockDomain_340bd7d4-af7d-4032-8ba9-991e246c3ded" xlink:to="loc_us-gaap_SeriesFPreferredStockMember_ef172e89-abe1-4f22-afd7-efcd2073257f" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SeriesBPreferredStockMember_4f5e234b-8d01-42b3-bf97-add0bb48ec4e" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_SeriesBPreferredStockMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockDomain_340bd7d4-af7d-4032-8ba9-991e246c3ded" xlink:to="loc_us-gaap_SeriesBPreferredStockMember_4f5e234b-8d01-42b3-bf97-add0bb48ec4e" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CommonStockMember_cbdba1af-f38f-4195-87bc-a3f38daf57c3" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_CommonStockMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockDomain_340bd7d4-af7d-4032-8ba9-991e246c3ded" xlink:to="loc_us-gaap_CommonStockMember_cbdba1af-f38f-4195-87bc-a3f38daf57c3" xlink:type="arc" order="6"/>
  </link:definitionLink>
</link:linkbase>
