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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 according to the year 2010 census), an (MSA) which includes all of Oconee County and which is further included in the greater Greenville-Spartanburg-Anderson, South Carolina Combined Statistical Area (population 1,266,995 according to the year 2010 census).

The Democratic Vice-Presidential candidate for 2004, former United States Senator from North Carolina, John Edwards, was born in Seneca. The city is the current home of United States Senator Lindsey Graham. It was named for the nearby Cherokee town of Isunigu, known to the English as "Seneca Town".

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