Seneca is a city in Oconee County, South Carolina, United States. The population was 8,102 at the 2010 census. It is the principal city of the Seneca Micropolitan Statistical Area, an (MSA) that includes all of Oconee County, and that is included within the greater Greenville-Spartanburg-Anderson, South Carolina Combined Statistical Area. Seneca was named for the nearby Cherokee town of Isunigu, which English colonists knew as "Seneca Town".

Oconee County is the westernmost county in the U.S. state of South Carolina. As of the 2020 census, the population was 78,607. Its county seat is Walhalla and its largest community is Seneca. Oconee County is included in the Seneca, SC Micropolitan Statistical Area, which is also included in the Greenville-Spartanburg-Anderson, SC Combined Statistical Area. South Carolina Highway 11, the Cherokee Foothills National Scenic Highway, begins in southern Oconee County at Interstate Highway 85 at the Georgia state line.