The area was originally part of the Cherokee Nation's protected grounds after the treaty of 1763 when the French & Indian War ended. The first white man to settle permanently in the area was Richard Pearis, who settled at the falls of the Reedy River sometime after 1770. Paris Mountain, the mountain overlooking the city, is named for him.
During the Revolution, the Cherokee (and Pearis) sided with the British. After a campaign in 1776, the Cherokee agreed to the Treaty of DeWitt's Corner ceding territory that includes present-day Greenville County to South Carolina. Greenville was originally called Pleasantburg. Greenville County was created in 1786, but was called Greenville District from 1800 until 1868. It is speculated that the name was likely taken for American Revolutionary General Nathanael Greene.