Mount Vernon Square station is located at the border of the neighborhoods of Downtown and Shaw in the northwestern quadrant of Washington.

Most prominent is the Washington Convention Center, although a number of smaller residential and commercial projects have been completed within the surrounding blocks.

To the southeast of the station is the Mount Vernon Triangle, a business improvement district (BID) seeing rapid mixed-use growth.

To the southwest of the station is the mixed-use CityCenterDC development project, which is home to luxury condominiums and luxury retail franchises such as Louis Vuitton, Moncler, Gucci, Hugo Boss, Tesla, Del Frisco's Double Eagle Steak House, Fig & Olive and other upscale dining and shopping destinations.

Since May 7, 2023, the northeastern terminus of the Yellow Line was truncated from Greenbelt to this station, following its reopening after a nearly eight-month-long major rehabilitation project on its bridge over the Potomac River and its tunnel leading into L'Enfant Plaza.