Prior to Maryland, Duffner served as the head coach at the College of the Holy Cross where he compiled a 60–5–1 record. At Maryland, Duffner compiled a 20–35 record. His most important legacy at Maryland has been in the record books; most of the Terps' longstanding single game, season, and career passing and receiving record were broken during his tenure. This was due to the implementation of his run and shoot offense and quarterbacks John Kaleo, Scott Milanovich, and Brian Cummings. However, his teams were notoriously weak on defense, frequently giving up points so fast that even his prolific offense couldn't keep up. Duffner's only winning season came in 1995 when the Terps finished with a 6–5 record and started with four consecutive wins.
After leaving Maryland, Duffner became an assistant with the Cincinnati Bengals from 1997 to 2002, where he served as linebackers coach and then defensive coordinator. From 2003 to 2005, he served with the Green Bay Packers. In early 2006, he was signed by the Jacksonville Jaguars as the linebackers coach. He was hired by the Miami Dolphins in January to be their LB Coach for the 2014 season. On October 15, 2018 Duffner was named as the new defensive coordinator of the Tampa Bay Buccaneers.