Mason had been defensive coordinator for Stanford since 2011. The Cardinal ranked fifth in the nation in sacks last season with 44 and was one of just five teams in the nation to give up less than 100 rushing yards per game.
He replaces James Franklin, who left the Commodores to become the new head coach at Penn State.
"I am so excited to be at Vanderbilt," Mason said. "This university combines the best of what's good about college athletics and academics. We expect to be competitive and look forward to competing for an SEC East crown."