Its northern terminus is at U.S. Route 54 between Collins and El Dorado Springs at the community of Cedar Springs; its southern terminus is at the Arkansas state line (north of Berryville, Arkansas) where it continues as Highway 221.

About one mile (1.6 km) before reaching Stockton, the road begins a brief concurrency with Route 32 before turning south again.

At the north edge of Mount Vernon is the western terminus of Route 174, and two miles (3 km) further south, Route 39 turns east, joining Business Loop I-44 for about two miles (3 km).

At Shell Knob, Route 39 crosses Table Rock Lake.

At Viola Route 39 enters Stone County and further south at Carr Lane is an intersection with Route 86, and one mile (1.6 km) further south the highway crosses the Arkansas state line.