South Carolina Highway 421 (SC 421) is a state highway in the U.S. state of South Carolina. It is an alternate route to U.S. Route 1 (US 1) and US 78 between North Augusta and Aiken.
SC 421 begins where it splits off from US 1/US 78 (Jefferson Davis Highway) southwest of Clearwater; 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. A majority of the highway is four-lanes that travels a total of .
SC 421 was established by 1952 as a renumbering of US 1/US 78, which was realigned onto new four-lane routing just north of it. The route has remained unchanged since inception.