George McDuffie (1788 - 11 March 1851) was a Governor of South Carolina and a member of the United States Senate.

Born in Columbia County, Georgia, McDuffie was admitted to the bar in 1814, and served in the South Carolina General Assembly in 1818-1821, and in the national House of Representatives in 1821-1834. In 1821 he published a pamphlet in which strict states' rights were strongly denounced; yet in 1832 there were few more uncompromising nullificationists.

The change seems to have been gradual, and to have been determined in part by the influence of John C. Calhoun. When, after 1824, the old Democratic-Republican party split into factions, he followed Andrew Jackson and Martin Van Buren in opposing the Panama Congress and the policy of making Federal appropriations for internal improvements. He did not hesitate, however, to differ from Jackson on the two chief issues of his administration: the Bank and nullification.

In 1832 he was a prominent member of the South Carolina Nullification Convention , and drafted its address to the people of the United States. He served as governor in 1834-1836, during which time he helped to reorganize South Carolina College . From January 1843 until January 1846 he was a member of the United States Senate. The leading Democratic measures of those years all received his hearty support. McDuffie, like Calhoun, became an eloquent champion of state sovereignty; but while Calhoun emphasized state action as the only means of redressing a grievance, McDuffie paid more attention to the grievance itself. Influenced in large measure by Thomas Cooper, he made it his special work to convince the people of the South that the downfall of protection was essential to their material progress. His argument that it is the producer who really pays the duty of imports has been called the economic basis of nullification. He died at Cherry Hill, South Carolina , on 11 March 1851.

McDuffie County, Georgia is named after him.