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 (population 74,273 at the 2010 census), an (MSA) that includes all of Oconee County, and that is included within the greater Greenville-Spartanburg-Anderson, South Carolina Combined Statistical Area (population 1,266,995 at the 2010 census). Seneca was named for the nearby Cherokee town of Isunigu, which English colonists knew as "Seneca Town".
In the antebellum period, this area was part of the Pickens District, South Carolina. The state had used jurisdictions such as parish, county, district, and county again in its history. Oconee County was not organized until 1868, after the American Civil War.
Seneca was founded in 1874, during the Reconstruction era, as the railroad town "Seneca City", named for the Seneca River and a historic Cherokee town known as Isunigu. It was called Seneca in a kind of transliteration by British colonists.
Seneca City was developed at the intersection of the Blue Ridge Railroad and the newly built Atlanta and Charlotte Air Line Railroad.