Born in Buck County, Pennsylvania, he moved to the Waxhaw settlement with his parents in 1752. He served in the provincial militia in the campaign against the Cherokees in 1760. During the Revolutionary War, Pickens attained the rank of brigadier general and led a partisan force in the backcountry credited with disruption of the occupying British forces. After the war Pickens served in the South Carolina House of Representatives and Senate. He also served in the United States House of Representatives from 1793-1795. Until his death in 1817 Pickens served in a variety of local elected offices including tax collector and commissioner of roads.