South Carolina Highway 125 (SC 125) is a 56.2-mile (90.4 km) state highway, connecting Allendale and Aiken counties through the Savannah River Site and providing a principal route between the Augusta region and the South Carolina Lowcountry. It is an alternate and more direct route to U.S. Highway 278.

The route travels generally in a southeast to northwest direction, beginning in downtown Allendale and ending in downtown North Augusta, one mile north of Augusta.

The route is primarily rural in nature. For an 18-mile (29 km) stretch, SC 125 runs through the southern portions of the Savannah River Site, where vehicles are prohibited from stopping (except for emergencies). Access to SRS facilities is regulated through several internal access roads that have checkpoints near the intersections with SC 125.