[citation needed] Graduating from South Carolina College in 1813, he was admitted to the bar in 1814, and went into partnership with Eldred Simkins at Edgefield.

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.

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.

[2]Benjamin Perley Poore wrote that McDuffie was a "spare, grim-looking man, who was an admirer of Milton, and who was never known to jest or smile.

"[3] His oratorical style, too, was "nervous and impassioned, and at times fiercely vehement," on one occasion even driving the famously combative John Randolph from the floor with "vituperation witheringly pungent".