 SC 421 begins where it splits off from US 1/US 78 (Jefferson Davis Highway) west of North Augusta; it immediately connects with US 278/SC 125 (Atomic Road).Heading northeast, it parallels US 1/US 78 to its south, going through the towns of Clearwater, Burnettown, Langley, Gloverville and Warrenville.Upon entering Aiken, it reconnects with US 1/US 78.