With the win, Vanderbilt (5-6, 2-5 Southeastern Conference) assured coach Derek Mason his best record yet in his third season. The Commodores now need a win in their regular season finale to become bowl eligible for the first time since 2013. Their APR is so good that five wins could be enough, winning a sixth game would be even better.
"Listen that's exactly what we're going to do," Mason said. "We're going to line ourselves up and try to get ourselves ready to go play one more game because that's what we're guaranteed. And you know what? We're looking forward to this one."
Kyle Shurmur threw for 273 yards and two touchdowns, and the Commodores also had three sacks. Linebacker Zach Cunningham, the SEC's leading tackler, recovered a fumble.
Vanderbilt was the first SEC opponent that Mississippi played this season that hadn't been ranked, and the Commodores snapped the Rebels' two-game win streak. Now the Rebels (5-6, 2-5) need a win in the Egg Bowl to extend its bowl streak.
Freshman Shea Patterson, so thrilling in rallying the Rebels to an upset at Texas A&M last week , struggled against Mason's defense. Ole Miss had to settle for a field goal on the opening drive, and Patterson added TD passes to Akeem Judd and Evan Engram.
The Rebels were held to a season-low in points, and Jason Pellerin replaced Patterson for the final drive. Ole Miss coach Hugh Freeze said they got beat on a big play before Vandy scored its first TD.
"And we never found the rhythm again offensively," Freeze said. "I don't know how many drops we had tonight. It had to be approaching 10 to 12, and those are critical."
The key play came within the opening minute of the third quarter and cost the Rebels their leading tackler, linebacker DeMarquis Gates, for a targeting even though a flag wasn't thrown.
The penalty was announced after the replay booth reviewed what appeared to be a fumble by Vanderbilt's Donovan Tennyson off a double reverse recovered by Ole Miss defensive back Tony Conner whose foot was out of bounds when he picked up the ball.
Vanderbilt finished off a 90-yard drive with Webb's second TD, an 11-yard run, and a 21-10 lead.
Mississippi: Patterson looked so dazzling in his debut at Texas A&M. But Mason defended the likes of Marcus Mariota while coordinator at Stanford, and that game gave Mason plenty to study of Patterson in the Ole Miss offense. At least the Rebels will be at home trying to become bowl eligible for a fifth straight season, something they haven't done since 15 straight bowls between 1957 and 1971.
Vanderbilt: Ole Miss' first TD came off a muffed punt by Darius Sims in the first quarter, the kind of mistake that has often soured the Commodores' fortunes. This time, they shook off the mistake with their best offensive performance against an SEC opponent in both points and yards (481).
Mississippi hosts Mississippi State in the Egg Bowl.
Vanderbilt hosts in-state rival Tennessee.