The western terminus of the route is in northwestern Choctaw County near the community of Yantley, where it serves as a continuation of Mississippi Highway 19 (MS 19).

West of its interchange with Interstate 65 (I-65) at exit 128 in Greenville, the route passes through the Black Belt, traditionally one of the poorer areas of the state.

SR 10 then passes through Luverne, Troy, and Abbeville, before reaching the Chattahoochee River at the Georgia state line, where it continues eastward as Georgia State Route 37.

There is a low (10 feet (3.0 m)) clearance under a railroad underpass in Greenville.

The truck route allows large vehicles to bypass the roundabout at the county courthouse downtown.