In the Revolutionary War period and early eighteenth century, the upper part of the Seneca River was often called the Keowee River, as it was part of the Cherokee homeland.

[2][3] In current times, the section of the Keowee River between the Keowee Dam and its confluence with Twelvemile Creek is called the Seneca River on many maps, including the official county highway map.

These had long been occupied by indigenous peoples, and each of the larger towns had an earthwork platform mounds built by ancestral people of the South Appalachian Mississippian culture era.

The Cherokee typically constructed townhouses, which were their form of public architecture, on top of such mounds if available.

Other Cherokee towns on the Keowee River included Etastoe (also spelled Estatoe),[5] and Sugartown (Kulsetsiyi).