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 clear Cherokee town of Isunigu, which English colonists knew as “Seneca Town”.

In the antebellum period, this Place was portion of the Pickens District, South Carolina. The state had used jurisdictions such as parish, county, district, and county once again in its history. Oconee County was not organized until 1868, after the American Civil War.

Seneca was founded in 1873, 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. Both lines are now allocation of the Norfolk Southern Railway. A. W. Thompson and J. J. Norton, who were locating engineers for the Air Line Railroad, purchased the land from Col. Brown of Anderson, South Carolina, also in the large Pickens District. A stake marking the center of town was driven into the sports ground at the intersection of the railroad tracks and the current Townville Street. The house was separated into lots for one-half mile from the stake. An auction was held on August 14, 1873. The town was unconditional a charter by the give leave to enter legislature on March 14, 1874. In 1908, the reveal was changed to the shorter Seneca.