| UAC | Unaccompanied Alien Children (changed to UC) |
| UAS | Unmanned Aircraft Systems Program, EPA | Unmanned Aircraft Systems Program, NOAA (changed to UxSRTO) |
| UASI | Urban Area Security Initiative |
| UAVSAR | Uninhabited Aerial Vehicle Synthetic Aperture Radar |
| UBPR | Uniform Bank Performance Report |
| UBT | Urban Bird Treaty |
| UC | Unaccompanied Children |
| UCDMO | Unified Cross Domain Management Office (unable to verify 12/13) |
| UCF | Urban and Community Forestry (older link archive) |
| UCMR | Unregulated Contaminant Monitoring Rule |
| UCR | Uniform Crime Reporting (older link archive; archive2; archive3; archive4) | Urban Congestion Reports |
| UCS | Unaccompanied Children's Services (unable to verify 2/21; older link archive) |
| UDC | Universal Data Collection System |
| UDI | Urban Dynamics Institute (unable to verify 9/20) |
| URCS | Uniform Rail Costing System |
| URDB | Utility Rate Database |
| URLPWC | Upholding the Rule of Law and Preventing Wrongful Convictions Program |
| URM | Unaccompanied Refugee Minors Program (older link archive) |
| URMCC | Utah Reclamation Mitigation and Conservation Commission |
| URS | Uniform Reporting System | Urban Rate Survey |
| USADF | United States African Development Foundation |
| USAFC | USA Freedom Corps (changed to Serve.gov; then CNCS; then AmeriCorps) |
| USAGM | U.S. Agency for Global Media |
| USAID | United States Agency for International Development |
| USALEEP | U.S. Small-area Life Expectancy Estimates Project |
| USAO | Offices of the United States Attorneys |
| USAP | United States Antarctic Program |
| USARC | U.S. Arctic Research Commission (also, ARCTIC) |
| USBC | Bureau of the Census |
| USBDC | U.S. Bomb Data Center |
| USBG | United States Botanic Garden |
| USBP | United States Border Patrol |
| USBR | Bureau of Reclamation |
| U.S.C. | United States Code (older link archive) |
| USCAVC | United States Court of Appeals for Veterans Claims |
| USCC | U.S.-China Economic and Security Review Commission |
| USCCR | United States Commission on Civil Rights |
| US-CERT | United States Computer Emergency Readiness Team (older link archive; archive2) |
| USCFC | U.S. Court of Federal Claims |
| USCIRF | United States Commission on International Religious Freedom |
| USCIS | U.S. Citizenship and Immigration Services |
| USCIS ELIS | USCIS Electronic Information System |
| US CLIVAR | US Climate Variability & Predictability Program |
| USCO | United States Copyright Office |
| USCP | U.S. Capitol Police |
| USCRN | U.S. Climate Reference Network (older link archive) |
| USCRTF | United States Coral Reef Task Force |
| USCS | United States Cancer Statistics (older link archive) | United States Customs Service (changed to CBP) |
| USDA | United States Department of Agriculture |
| USDFRC | U.S. Dairy Forage Research Center |
| USDS | United States Digital Service |
| USDSS | United States Diabetes Surveillance System |
| USEER | U.S. Energy and Employment Report |
| USEITI | United States Extractive Industries Transparency Initiative (redirects to revenuedata.doi.gov as of 11/17; older link archive) |
| USES | United States Employment Service (defunct) |
| USFA | U.S. Fire Administration |
| USGCRP | U.S. Global Change Research Program |
| USGEO | U.S. Group on Earth Observations (older link archive) |
| USGM | United States Government Manual |
| USGS | United States Geological Survey |
| USHCN | U.S. Historical Climatology Network (older link archive; archive2) |
| USHIK | United States Health Information Knowledgebase (older link archive) |
| USHMC | U.S. Housing Market Conditions |
| USHMM | United States Holocaust Memorial Museum |
| USHRL | U.S. Horticultural Research Laboratory |
| USIA | United States Information Agency (changed to IIP) |
| USIBWC | U.S. Section of the International Boundary and Water Commission |
| USICH | United States Interagency Council on Homelessness |
| USICN | U.S. International Competition Network (unable to verify 9/16) |
| USINT | U.S. Interests Section (replaced by U.S. Embassy Cuba; see archive) |
| USIP | United States Institute of Peace |
| USITC | United States International Trade Commission |
| USJC | Judicial Conference of the United States |
| USLM | United States Legislative Markup |
| USMARC | U.S. Meat Animal Research Center |
| USMCA | United States-Mexico-Canada Agreement |
| USRT | U.S. Radiologic Technologists Study (older link archive) |
| USSC | United States Sentencing Commission |
| USSG | United States Sentencing Guidelines |
| USSGL | U.S. Standard General Ledger (older link archive) |
| USSP | United States Support Program |
| USSS | United States Secret Service |
| UST | Underground Storage Tanks |
| USTDA | United States Trade and Development Agency |
| USTP | U.S. Trustee Program |
| USTR | United States Trade Representative |
| USUN | United States Mission to the United Nations (older link archive) |
| US-VISIT | U.S. Vistor and Immigrant Status Indicator Technology (replaced by OBIM) |
| USWDS | U.S. Web Design System |
| USWTDB | United States Wind Turbine Database |
| UTC | University Transportation Centers (older link archive) |
| UV-CDAT | Ultrascale Visualization Climate Data Analysis Tools |
| UVL | Unverified List |
| UWFP | Urban Waters Federal Partnership |
| UWR | United We Ride (older link archive) |
| UxSRTO | Uncrewed Systems Research Transition Office |
