South Carolina Highway 421 (SC 421) is a highway in Aiken County, South Carolina. It runs 10.5 miles (16.9 km) in length.

SC 421 begins where it splits off from the Jefferson Davis Highway (U.S. Route 1/U.S. Route 78) near the city of North Augusta, just south of an interchange with U.S. Route 278 and SC 125. The highway then heads northeast, paralleling the Jefferson Davis Highway, before intersecting SC 126 in the town of Clearwater. In the town of Warrenville, SC 421 intersects SC 191, then it turns more easterly, before ending back at the Jefferson Davis Highway, approximately four miles west of the city of Aiken.

The entire route is in Aiken County.