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 th…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 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".