He made his debut in 1963 at Myrtle Beach Speedway, finishing 12th out of 18 drivers. He went on to finish in the top ten in points twice in his career and won the pole position for the 1978 Delaware 500. He fielded his own team for most of his career. His underfunded efforts made him a fan favorite, especially as his career ran down and he only ran selected races. McDuffie was involved in an accident in the opening laps of the 1991 Bud at the Glen race at Watkins Glen International Raceway. He lost control of his car in turn 5, slammed the tire barrier at the end of the corner, and flipped upside down onto fellow competitor and independent Jimmy Means' car. Means made it out unscathed, but McDuffie did not survive the wreck. McDuffie's fatal wreck, and a serious injury to Tom Kendall six weeks earlier in the Camel Continental VIII, led to a new bus stop chicane shortly before Turn 5 to slow down the speeds entering the turn.
J.D. McDuffie is still the record holder for most starts in NASCAR's top touring series without recording a win. His 653 starts ranks 14th all time (as of May 7, 2006).