US 50 enters the District of Columbia from Arlington, Virginia, merging with I-66 on the Theodore Roosevelt Bridge over the Potomac River.
Near the National Gallery of Art, US 50 turns left onto 6th Street NW, and after several blocks, right onto New York Avenue.
The northern terminus of I-395 is at a signaled intersection with New York Avenue and 4th Street NW.
US 1 Alternate is concurrent with US 50 along New York Avenue between 6th Street NW and Bladensburg Road.
US 50 then crosses the Anacostia River and continues into Maryland, where it becomes the John Hanson Highway and intersects the Baltimore-Washington Parkway.