The winner served as redemption for Gano, who missed an extra point in the third quarter.
It was the second home loss this season for the usually unbeatable Patriots at Gillette Stadium. The defeat marked just the second time since 2012 that Tom Brady has lost two home starts within a season.
Cam Newton threw for three touchdowns and ran for another . Jonathan Stewart rushed 14 times for 68 yards to pass DeAngelo Williams and become the franchise’s all-time leading rusher.
Newton finished 22 of 29 for 316 yards and an interception, picking apart a New England defence that was giving up an NFL-worst 461 yards and 31.7 points per game. The Patriots forced a pair of turnovers, but had trouble containing Newton’s stable of targets.
Carolina (3-1) finished with 444 total yards, marking the fourth straight game the Patriots have given up at least 300 yards.
Brady finished 32 of 45 for 307 yards and two scores.
The Patriots cut a 30-16 deficit in half on an 8-yard run by Dion Lewis with 8:46 remaining. Linebacker Dont’a Hightower forced a punt on Carolina’s next drive when he sacked Newton on third down.
Brady then found Danny Amendola in the back of the end zone on fourth-and-goal from the 1 to tie the game. But two penalties on New England’s defence on the Panthers’ final drive set up Gano’s winner.
Newton mostly had his way with the Patriots in the opening 30 minutes as the Panthers took a 17-16 lead into the locker room. He led them to a field goal on their first series of the game, completing passes of 14, 2 and 13 yards.
Newton tried to get too creative on their second drive, tossing into double coverage. He was intercepted by Malcolm Butler.
But after the Patriots took a 10-3 lead on a 2-yard pass from Brady to Chris Hogan, Newton led Carolina on a six-play, 75 yard drive capped by a 28-yard touchdown on a screen pass to Fozzy Whittaker .
He was spot-on again late in the half, leading Carolina on a nine-play, 84-yard drive that ended with a 10-yard strike to Devin Funchess.
New England was able keep pace thanks to three first-half field goals by Stephen Gostkowski. It included a team-record 58-yarder as time expired in the second quarter.
Panthers: S Kurt Coleman left in the second quarter with a knee injury and did not return; WR Damiere Byrd left in the second quarter with a forearm injury and also did not return; Funchess limped off late in the fourth quarter.
Patriots: S Eric Rowe exited the game in the third quarter with a groin injury; LB Elandon Roberts left with a groin injury.
Panthers: Play at Detroit on Sunday.
Patriots: Play at Tampa Bay on Thursday night.