From Atlanta, GA
There are three routes you can take from Atlanta: I-85 North through Anderson (S.C.); I-20 East to Thompson (Ga.) and McCormick (S.C.); or through Athens to S.C. 72. There is little time difference, although most people seem to prefer the I-85 route.
Printable directions from Atlanta via I-85.
From Charlotte, NC
There are two routes to take from Charlotte: via I-77 and Chester or via I-85 and Spartanburg. The drive via Chester is shorter but is mostly two-lane roads. The route through Spartanburg is longer but is mostly interstate driving. Both routes take about the same driving time.
From Columbia, SC
There are two routes to take from Columbia: via Saluda or via Newberry. The drive through Saluda is fewer miles but takes longer than the route through Newberry, which is more interstate and highway driving.
Printable directions from Columbia via I-26 through Newberry.