[6] It was named after Andrew Pickens (1739–1817), an American revolutionary soldier and US Congressman for South Carolina.

In 1791, the state legislature established Washington District that comprises present-day Greenville, Anderson, Oconee, and Pickens Counties.

A courthouse was established on the banks of the Keowee River where the town of Pickens Court House was developed.

The Hagood-Mauldin House was built circa 1856 and is one of the historic structures of Pickens County.

Until they were banned in the US, Sangamo discharged a significant amount of polychlorinated biphenyls (PCBs) into a tributary of the Twelve Mile River which feeds into Lake Hartwell.

Schlumberger paid $11.8 million to federal and state agencies for injuries to natural resources caused by the contamination.

Sixty-five acres of the mountain are part of the South Carolina Heritage Trust, and contain varied and rare plant species.

[citation needed] As of the 2020 United States census, there were 3,388 people, 1,190 households, and 764 families residing in the city.

Located three miles north of downtown on US 178 is Hagood Mill, listed on the National Register of Historic Places since 1972.

There are monthly southern heritage festivals at the site, and stone ground corn meal and grits may be purchased.

It was constructed in 1903 and served as a detention facility and offices and living quarters for the county sheriff.

The School District of Pickens County is headquartered in Easley, a neighboring city.