The second-year quarterback threw for 253 yards and ran for a career-high 71 yards and led the Panthers to a 35-27 win over New Orleans and leaving the NFC South champion Saints 0-2 for the first time since 2007.
"Times change," wide receiver Steve Smith said of Carolina's first win over New Orleans since 2009.
Coach Ron Rivera said a loss to Drew Brees and the Saints would have been tough to take, especially with a tough game coming up Thursday night against the Super Bowl champion New York Giants.
"The way we responded as a team this week was outstanding," Rivera said. "I think the attitude, the effort was great."
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The Panthers tied a club record last week with 10 yards rushing in a loss to Tampa Bay.
They had no such problems moving the ball against the Saints. They got the running game going in the second quarter and rolled up 219 yards on the ground and 463 overall.
Newton kept the Saints off balance all day, running eight times for 66 yards in the first half as coordinator Rob Chudzinski used a variety of plays that allowed Carolina to take a 21-13 halftime lead.
"You do read option, read option, read option and then get them to play seven or eight in the box and you've got so many variations of plays and passes you can run off that," Newton said.
Added Tolbert: "The zone read was one of the plays that we saw on film that they was kind of vulnerable to. It was working so we stuck with it. They weren't fitting the gaps right on that play."
When the Saints began to figure things out, Newton would find open receivers who beat one-on-one matchups on the outside.
On one second-half play there was not a defender within 20 yards of Smith when he hauled in a pass from Newton along the right sideline and raced 66 yards before being dragged down.
"I was shocked just as much as anybody," Newton said. "Of all of the people on this field to be wide open, you would think Smitty would be the last person. But that is what type of pressure the zone read gives us."
Panthers tackle Jordan Gross said bouncing back from last week's poor offensive outing was big. Gross said he has never been on a team that has run the ball as poorly as the Panthers did last week.
"We played like we're capable of," Gross said. "I would expect days like this to be the standard, not last week."
The Saints, meanwhile, have serious concerns on defense.
They've allowed 922 yards and 75 points in two games against Newton and Robert Griffin III.
"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," said interim coach Aaron Kromer, who is running the team because coach Sean Payton and assistant head coach Joe Vitt are serving suspensions for their roles in the Saints' bounty scandal. "So do we have to do better against those styles of offenses? Yeah, we do.
"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."
Brees came in having won five straight starts against Carolina.
He threw for 325 yards, but was intercepted twice, including once by Charles Godfrey, who returned it 9 yards for a touchdown. The Panthers only sacked Brees once but pressured him into getting rid of the ball early several times. Brees was twice flagged for intentional grounding.
Brees briefly appeared to be hurt in the third quarter when defensive end Greg Hardy collapsed the pocket on came crashing down on his leg from behind. Brees hobbled off the field but returned for the next series, never missing a play.
"It's fine," Brees said. "It just got rolled up on in an awkward position."
Brees got off to a good start by completing all six passes for 55 yards on the Saints' opening drive, including a 1-yard touchdown pass to Jimmy Graham. After converting just two of 11 third-down conversions last week against Washington, the Saints seemed to rectify that problem on the game's opening drive.
But Carolina's defense came back on the next possession when Godfrey stepped in front of a rollout pass by Brees and returned it for a score to tie the game.
Jon Beason also intercepted Brees on the final drive to seal the win.
The last time the Saints started 0-2 was five years ago when they finished 7-9 and failed to make the playoffs.
They'll look to rebound next Sunday at home against Kansas City.
"The challenge now is keeping from that mentality of why it's happening, or pointing fingers and saying 'this guy isn't doing what he's supposed to,"' said Saints tackle Zach Strief. "That's dangerous. That's poisonous to a locker room."
- The Panthers are 6-1 over the past two seasons in games in which Newton does not throw an interception.
- Smith was carted to the locker room at one point in the third quarter after reinjuring his knee, but returned to the game. He said afterward he's fine.
- Pierre Thomas had 110 yards rushing for the Saints and Darren Sproles had 13 catches for 128 yards receiving.
- Charlotte Bobcats owner and former NBA great Michael Jordan took in the game from a luxury suite.