George McDuffie graduated from South Carolina College and was admitted to the bar in 1814. He began his political career in the South Carolina General Assembly and later served in the United States House of Representatives. McDuffie transitioned to the governorship of South Carolina and held a significant military position as a major general of the South Carolina Militia. He also served in the United States Senate, where he aligned with the Democratic Party and opposed certain federal policies. McDuffie's career was marked by his evolving stance on states' rights and his involvement in notable political actions, including an impeachment trial.

George McDuffie's political career is marked by an intriguing ideological evolution, shifting from denouncing strict states' rights to becoming a prominent nullifier. His opposition to the 1828 Tariff of Abominations highlights a calculated approach to protecting regional economic interests. McDuffie's rhetorical style, described as "nervous and impassioned," reveals a deeply committed, if not volatile, approach to public speaking. His unexpected alignment with Democratic measures in the Senate, despite his earlier stances, suggests an ideologically agile politician who navigates complex political landscapes with strategic precision.