SC 154 begins at an
intersection with
U.S. Route 76 (US 76; Florence Highway) in Mayesville, within
Sumter County, where the roadway continues as Mayes Open Road. It travels to the north-northwest and enters
Lee County. In
St. Charles, it intersects
US 401 (Darlington Highway). The highway passes Lower Lee Elementary School and goes through
rural areas of the county. It passes over, but does not have an
interchange with
Interstate 20. A short distance later, it enters Bishopville, where it meets its northern terminus, an intersection with
US 15 (Sumter Highway).[3]