He attended the University of Notre Dame, and played for coach Ara Parseghian and coach Dan Devine's Notre Dame Fighting Irish football team from 1975 to 1979. As a junior, Huffman was a member of the Irish's 1977 national championship squad. As a senior in 1977, he was recognized as a consensus first-team All-American. His brothers, Tim and Steve, also played for Notre Dame. He was noted for his good humor, which included saying that during games he always wore red-colored elbow pads so that his mother could see where he was in the pile-ups.
The Minnesota Vikings selected Huffman in the second round (forty-third pick overall) of the 1979 NFL Draft, and he played for the Vikings from 1979 to 1990 with only one interruption. In 1984 and 1985, he also played for the USFL's Arizona Wranglers and Memphis Showboats. In his eleven NFL seasons, he played in 128 games.
Huffman died in a car accident November 21, 1998, while on his way to the final Notre Dame home game of the seasons. He was driving drunk after being out at Chicago bars and thankfully his passenger was not killed. He was survived by his wife, Cathy, a daughter, Jessica, and a son, Jack. Each year, the city of Chanhassen, Minnesota, where Huffman served as a Park & Recreation Commissioner after his playing days, hosts a Dave Huffman Memorial 5,000-meter run.