It was named for Revolutionary War hero Elijah Clarke and included 250 square miles (647.5 km2) that was formerly part of Jackson County.

Colonel Clarke played a leading role the 1779 victory at the Battle of Kettle Creek in Wilkes County.

The Elijah Clarke Chapter of the Daughters of the American Revolution erected a monument to him in Broad Street in Athens.

Manufacturing and textile production operations were the major industries in Clarke County, especially after the railroad reached Athens in 1841.

Two skirmishes were fought in Clarke County in 1864, during the American Civil War, one near Barber's Creek and the other near Mitchell's Road.

As an extension of the state, the county would conduct welfare and health programs, build and maintain roads, and hold courts of law.

[18] Due to the presence of the University of Georgia campus in Athens,[19] Clarke County has long been a Democratic Party stronghold in presidential elections.