Brees passed for 396 yards, giving him 5,177 this season. That makes him the first player to eclipse 5,000 yards three times. His four TD passes gave him 43 in 2012, and he's the first player with 40 TD passes in consecutive seasons.
The Saints (7-9) also gave up 530 yards, raising their season total to 7,042 to break the old record of 6,793 allowed by the 1981 Baltimore Colts.
Carolina kicker Graham Gano had field goals of 20, 31 and 42 yards.
Cam Newton was 16 of 33 for 248 yards and was intercepted once by Jonathan Vilma, a central figure in the bounty scandal who was initially suspended the entire season. But he never served a game of that ban after he, defensive end Will Smith, and former Saints Scott Fujita and Anthony Hargrove fought successfully to have their suspensions of various lengths thrown out on appeal.
The Superdome crowd was exuberant after Vilma labeled by the NFL as a ringleader in the Saints' cash-for-hits program returned the interception 18 yards for a touchdown that gave the Saints a 14-10 lead. The Panthers were the ones celebrating in the end as they finished strong for coach Ron Rivera, who has been fielding questions about his job security after a pair of losing seasons.
In the fourth quarter, Newton appeared to injure his lower left leg. It was caught awkwardly under defensive end Turk McBride on a hit shortly after Newton had delivered a throw. But Newton returned after missing several plays to complete a touchdown drive.
Leading 24-13, the Saints looked ready to seize control in the third quarter. Panthers tight end Greg Olsen fumbled along the sideline in Carolina territory, and Saints defensive back Johnny Patrick appeared to recover it. Initially, the play was blown dead and Olsen ruled down. Saints assistant head coach Joe Vitt challenged the call, and the play was ruled a fumble, but Patrick's right foot was so close to the sideline that referee Al Riveron could not determine if the Saints took possession.
The ball remained with the Panthers, and Williams ran for his long TD soon afterward. That cut the deficit to 24-20, and Carolina took a 27-24 lead after converting Brees' 19th interception of the season into Tolbert's second short scoring run. Safety Charles Godfrey picked off an underthrown pass that had Brees ripping at his chin strap in disgust.
Two of Brees' scoring passes went to Marques Colston for 7 and 9 yards. He also hit tight end Jimmy Graham for a 19-yard score and Darren Sproles for a 33-yard TD in the fourth quarter as the Saints, who trailed 41-24 with 8:23 left, nearly mounted a late comeback.
Lance Moore had four catches for 121 yards and Graham had nine catches for 115 yards. Both players surpassed 1,000 yards receiving on the season, joining Colston, who eclipsed the mark a week earlier in Dallas.