The Carolina Panthers trio of Cam Newton, DeAngelo Williams and Jonathan Stewart ran through a plethora of gaping holes and handed the New Orleans Saints their first 0-2 start since 2007.
Newton, Williams and Stewart helped the Panthers total 219 yards rushing in Carolina's 35-27 win over the Saints.
Down by eight with 48 seconds left and no timeouts, the Saints got the ball at their own 20-yard line, but Jon Beason intercepted Drew Brees' pass over the middle with 23 seconds remaining to seal the win.
Newton carried the ball 13 times for a career-high 71 yards and a touchdown, Williams ran for 69 yards and a score on 14 rushes and the returning Stewart, who missed the opener with a right ankle injury, added 51 yards on the ground.
Newton also threw for 253 yards with a touchdown on 14-of-20 efficiency, while Steve Smith caught three balls for 104 yards for Carolina (1-1), which fell to the Tampa Bay Buccaneers in its opener.
"The way we responded as a team this week was outstanding," Panthers head coach Ron Rivera said. "I think the attitude, the effort was great."
Brees was 31-of-49 for 325 yards with a touchdown and two interceptions for New Orleans (0-2), which began the 2007 campaign 0-4 before finishing 7-9.
Darren Sproles had 13 receptions for 128 yards, while Jimmy Graham totaled 71 yards receiving with a touchdown on seven catches in defeat.
New Orleans' defense has surrendered 75 points and 922 yards in two games.
"If you look at our defense, and you look at the two offenses we've played, we've played the most unconventional offenses in the National Football League," Saints interim coach Aaron Kromer said. "One thing we need to get settled in on is on that style. But we've played two good offenses, and we just need to keep working at it and plugging away."
After Garrett Hartley booted a career-long 53-yard field goal, which gave the Saints a 13-7 lead early in the second quarter, Carolina tallied 21 unanswered points to seize control of the contest.
Smith hauled in a 35-yard completion down the left sideline on a 3rd-and-15 before Stewart took a screen for a 17-yard score, which capped an 8-play, 74- yard drive.
Following a Saints three-and-out, Brandon LaFell, who had six catches for 90 yards, took an end around 25 yards on the first play of Carolina's ensuing series. He added a 19-yard reception on a 3rd-and-10 before Mike Tolbert finished the 8-play, 58-yard trek with a two-yard TD run with 14 seconds left in the opening half.
After the teams exchanged punts to start the second half, Carolina went 80 yards in six plays and took a 28-13 advantage.
Stewart had a 16-yard run and Williams added a 27-yard scamper before Patrick Robinson was whistled for a pass interference at the 3-yard line while defending Smith, which led to a Williams TD run on the very next play.
In the fourth, a 29-yard completion to Marques Colston on a 3rd-and-6 led to a Mark Ingram one-yard TD plunge, but Carolina got the score back on its next touch to regain its 15-point bulge.
Smith was left unaccounted for along the right sideline on the first play of the drive and picked up 66 yards, which led to a Newton five-yard TD run off the left side for a 35-20 Panthers advantage.
Brees snuck in from a yard out with 1:59 left to make it 35-27, but Carolina recovered the ensuing onside kick. New Orleans' defense forced a three-and- out before Beason intercepted Brees' pass over the middle, which sealed the win for Carolina.
Earlier, Sproles caught five passes for 54 yards on the Saints' opening drive of the game, which culminated on a Graham one-yard TD reception.
On New Orleans' next touch, Brees tried to hit Graham for a screen on a play- action bootleg to the right, but Charles Godfrey jumped in front of Graham, intercepted the pass and returned it nine yards for the score.
Hartley booted through a 22-yard field goal on the Saints' ensuing possession, which gave the visitors a 10-7 edge late in the opening frame.
Brian Stropolo was taken off his scheduled duties as a side judge because photos on his Facebook page prominently showed him wearing Saints apparel. Stropolo worked the season-opening game between the New York Giants and Dallas Cowboys in New Jersey ... The Saints outgained the Panthers, 486-463 ... Ingram carried the ball 16 times for 53 yards ... It's Carolina's first win over the Saints since 2009.