Known as Prospect Road, the state highway runs 3.31 miles (5.33 km) from MD 543 near Ady north to MD 136 at Prospect.

Cherry Hill Road heads west from the other side of MD 543 as a county highway toward Rocks State Park.

MD 646 heads northeast as a two-lane undivided road through farmland.

After crossing Broad Creek, the state highway passes through the Mill Green Historic District, where it intersects Mill Green Road.

Prospect Road continues north as a county highway toward the Pennsylvania state line.