Pickens was educated at the University of Georgia in Athens, Georgia, and at South Carolina College in Columbia. He was admitted to the bar in 1829, the same year that he constructed "Edgewood," a mansion in Edgefield. He joined the Democratic Party and served in the South Carolina house of representatives from 1832–1834, where he was an ardent supporter of nullification. As chairman of a sub-committee, he submitted a report denying the right of Congress to exercise any control over the states.
Pickens served in Congress as a representative from South Carolina from 1834 until 1843 (5th District 1834–37; 6th District 1837–39; 5th District 1839–41; 6th District 1841–43). He was a member of the South Carolina state senate from 1844 until 1846. He was offered the position of Minister to England by PresidentJames K. Polk, and the Minister to France by President John Tyler, but declined these diplomatic posts. He served as a delegate to the Nashville Southern Convention in 1850. Twice a widower, he married Lucy Petway Holcombe (1832–1899) on April 26, 1856. Under President James Buchanan, Pickens was Minister to Russia from 1858–1860, where he and his wife were befriended by CzarAlexander II.
Under his administration as Governor of South Carolina (1860–1862), the state seceded and demanded the surrender of the Federal forts in Charleston harbor. He strongly advocated the secession of the Southern states and signed the South Carolina ordinance of secession. He protested against Major Robert Anderson's removal from Fort Moultrie to Fort Sumter, and offered to buy the fort from the Federal government. On January 9, 1861, Governor Pickens sanctioned the firing upon the relief steamshipStar of the West, which was bringing supplies to Anderson's beleaguered garrison. He also approved of the subsequent bombardment of Fort Sumter. He remained a fervent supporter of states rights.
