He graduated from South Carolina College in 1826 and studied law, but he did not practice. He made a financial success of his family's plantations in South Carolina and Mississippi. Hampton felt that the states of the South had the right to secede, but he questioned the institution of slavery and was concerned about the economic consequences of secession. He held several small public offices.
When South Carolina seceded, Hampton joined the Confederacy and was commissioned as a Colonel. He raised a command of cavalry, which was known as the Hampton Legion.
Hampton trained the cavalry troops to fight on foot when the Confederacy faced a shortage of horses. Hampton led troops to support Gen. Joseph E. Johnston's retreat through South Carolina. Since he and his troops were not actually under Johnston's command, Hampton did not have to surrender. He had considered following President Jefferson Davis and crossing the Mississippi River to continue resistance in Texas, but never did.
After the war, Hampton returned to his family's estates, which were ruined, and was able to restore them to their precious financial success. Politically, he strongly opposed the Radical Republicans, and was elected governor of South Carolina in 1876 and 1878. He was then elected to the Senate, in which he served until 1891.
When the Populists defeated Hampton's "Old South" party, Hampton ended his political career.