Known as River Road, the state highway runs 13.53 miles (21.77 km) from a dead end near Bertrand north to SR 3 near Litwalton in western Lancaster County.

SR 354 begins at a dead end on Whitehouse Creek, an estuarine tributary of the Corrotoman River.

SR 354 passes through the hamlets of Bertrand, Senora, and Ottoman, the last the site of a free ferry across the Western Branch.

North of Mollusk, the state highway meets the southern end of SR 201 (White Chapel Road).

SR 354 continues through Somers, which lies between Nuttsville to the east and Belle Isle State Park to the west on the Rappahannock River.