Cabinet Departments have headquarters or large office complexes in the area, including the Agriculture (including the former Cotton Annex and a building dedicated to the Forest Service), Transportation, HUD, Health and Human Services, Education, and Energy Departments.

The most prominent are the Department of Agriculture, which is housed in a neoclassical building complex that lines both sides of Independence Avenue, and the arcing high-rise of HUD, which is characterized by a unique installation of illuminated fiberglass rings in its 7th Street plaza.

The few non-governmental businesses in the neighborhood include five hotels, St. Dominic's Catholic Church, a few restaurants, a power station for the neighborhood, the First District police station, and commercial spaces (e.g., convenience stores, bank branches, coffee shops, etc.)

Also, L'Enfant Plaza, a multi-building complex and promenade that includes both government and civilian offices (as well as an indoor shopping mall), is located off Independence Avenue.

The Southwest Federal Center is served by the Smithsonian and Federal Center SW Metro stations on the Orange, Blue, Silver Lines, and by the L'Enfant Plaza station on the Green, Yellow, Silver, Orange, and Blue Lines.