One segment of 21.76 miles (35.02 km) runs from Highway 130 east of Almyra north to U.S. Route 79 (US 79) in Roe.

A fourth segment of 17.34 miles (27.91 km) runs from US 64 in Augusta north to Highway 37 east of Tupelo.

The route forms a 1.0 mile (1.6 km) concurrency with Highway 146 before turning north toward Monroe County.

The route serves as the western terminus for Highway 366 before entering the town of Roe, where it terminates at US 79.

The route begins at US 79 north of Roe and runs northwest, passing the Clarendon Municipal Airport before exiting Prairie County northbound.

The route begins at US 70 in Fredonia (Biscoe) and runs north, interchanging with Interstate 40 (I-40) and passing agricultural land on the west side of the road and the Cache River National Wildlife Refuge to the east.

[4] Upon entering Woodruff County, the route continues north along the western edge of the Cache River NWR, encountering Highway 262 twice and passing through Gregory.

Highway 33C passes the Ferguson House, Augusta Presbyterian Church and Woodruff County Courthouse, all listed on the National Register of Historic Places before turning onto Magnolia Street, passing the Augusta Memorial Park, turning onto 5th Street, and terminating at US 64.