The highway runs 10.43 miles (16.79 km) from the District of Columbia boundary in Chillum north and east to U.S. Route 1 (US 1) near Beltsville.

MD 212 connects the northern Prince George's County communities of Chillum, Langley Park, Adelphi, Hillandale, Calverton, and Beltsville.

Riggs Road continues into Washington, D.C. as a four-lane undivided highway to its southern end at North Capitol Street and Missouri Avenue.

MD 212 heads northeast along Riggs Road, which is a four-lane divided highway with bike and parking lanes.

A short distance north of Eastern Avenue, the highway intersects Chillum Road, which heads east as MD 501.

[1][2] MD 212 crosses the Northwest Branch of the Anacostia River at the site of the historic Adelphi Mill.

MD 212 continues northeast along Powder Mill Road, which passes the U.S. Army Research Laboratory and crosses Paint Branch.

A short distance southeast of the intersection, Powder Mill Road again becomes state maintained as MD 212A, which passes through the center of Beltsville.

[8][10] The highway followed a straight path, using what are today Cook Road and Prince Georges Avenue east and west of its at-grade Baltimore and Ohio Railroad crossing, respectively.

[23][24] MD 212 was also expanded to a divided highway from Beltsville Drive to Old Gunpowder Road when the I-95 interchange was built in 1971.

The highway veers southeast and crosses Indian Creek before reaching its eastern terminus at Edmonston Road.

Powder Mill Road continues east as a federally maintained highway through the Beltsville Agricultural Research Center.