With the game tied at 34 and the Blue Devils working on the clock while setting up for a potential go-ahead field goal, Josh Snead fumbled on a second-and-goal at the Cincinnati 5-yard line and the Bearcats recovered.
Four plays later, game MVP Brendon Kay connected on an 83-yard touchdown pass to tight end Travis Kelce to help lift Cincinnati to a 48-34 victory in the Belk Bowl.
"It's heartbreaking, because we wanted to win this game for our seniors," Snead said. "But as a team, we're going to learn from this and build off the momentum from this."
After the game, Duke coach David Cutcliffe refused to pin the loss on Snead, saying there were numerous missed opportunities.
Snead said he'll move on and learn from the mistake.
"I've got great teammates," Snead said. "They encouraged me to keep my head up. If you have a little adversity, you've got to face it. I'm one of the leaders on the team, and I can't show myself being down. I know my team's got my back. We just need to build off this. We've got to come back out in 2013 with this in the back of our head. It's going to help me grow as a man, too. You really can't learn from winning; you can learn from losing. We can learn from this."
As for the fumble, he couldn't explain what happened.
"The exchange to my handoff carrying the ball, it just popped out," Snead said. "Somebody got their hand in there and it popped out."
Kay threw for 332 yards and his four scoring passes were a Belk Bowl record.
His biggest TD pass came when Kelce got behind the Duke defense on a seam route, caught the ball in stride and raced the final 60 yards to the end zone as Blue Devils fans looked on in stunned silence.
Cincinnati (10-3) sealed it on the next series when Maalik Bomar came crashing into Duke quarterback Sean Renfree, forcing a deflection that Nick Temple returned 55 yards for a touchdown.
Renfree threw for 358 yards — another Belk Bowl record — for the Blue Devils (6-7). Conner Vernon, the ACC's all-time leader in receptions and receiving yards, had 10 catches for 119 yards and a touchdown in his final game for the Blue Devils.
Duke, which came in having allowed 51 points and an average of 294.5 yards rushing over its previous four games, struggled to stop Cincinnati after the first quarter.
The Bearcats piled up 554 total yards of offense, including 130 yards on the ground by George Winn. Duke wasn't too shabby on offense, either, combining with the Bearcats for a Belk Bowl-record 1,114 yards.
Kay's MVP performance comes after a career beset by injuries, but this turned out to be his night to shine.
The Bearcats trailed 16-0 before rattling off 27 straight points to seemingly take control, and the big turning point came from Cincinnati linebacker Greg Blair.
With Duke leading 16-3 and looking for more, Renfree fired a pass over the middle for running back Jela Duncan, who lunged for the goal line but was hit by Blair and fumbled. Blair recovered and suddenly the Bearcats had a shot.
Cincinnati came to life a short time later when Kay connected on a 25-yard touchdown pass to Anthony McClung, cutting the Duke lead to 16-10. Kay's second scoring pass, a 41-yard strike to Abernathy, capped a 98-yard drive in the final two minutes of the first half and gave the Bearcats their first lead.
Cincinnati carried the momentum into the second half, scoring on their first two possessions. Tony Miliano connected from 25 yards out and Winn cut back against the grain and raced 46 yards for his 13th touchdown of the season.
But the Blue Devils stormed back to take the lead on a 10-yard touchdown pass from Renfree to Vernon and a 2-yard pass from reserve quarterback Brendon Connette to David Reeves.
The game went back and forth from there before Kelce, who finished with 123 yards receiving, put the Bearcats ahead for good.
NOTES: Duke punter Will Monday set a Belk Bowl record with a 79-yard punt. ... The two teams set a combined record for most first downs in the Belk Bowl.