Maine Avenue begins at 17th Street SW and Independence Avenue SW and continues southeast, parallelling the Tidal Basin to 12th Street SW where it crosses under Interstate 395.

Continuing southeast, it runs parallel to the Washington Channel and Water Street SW, where it crosses 7th Street.

Points of interest along Maine Avenue include Arena Stage and the Southwest Waterfront, home of the Maine Avenue Fish Market.

In 1861, Maine Avenue was a small street north and parallel to Maryland Avenue near Capitol Hill.

That project, like many proposed interstate highways in the District of Columbia, was canceled.