Steve Smith caught the go-ahead touchdown pass and his long catch and run set up the clinching score and the Carolina Panthers used a ferocious defense to stifle Favre, Adrian Peterson and the Vikings in a 26-7 victory.
Hours after clinching the NFC North when Green Bay lost, the Vikings (11-3) failed to move within a game of NFC-leading New Orleans a night after the Saints' first loss of the season.
Surprisingly, the best quarterback on the field wasn't the 40-year-old Favre, but Matt Moore. In his third start for the injured Jake Delhomme, Moore threw for a career-high 299 yards and three touchdown passes.
"You saw a young guy mature," Smith said.
A four-time Pro Bowl pick, Smith had been quiet most of the season with Carolina's quarterback woes. But he caught nine passes for 157 yards and keyed Carolina's 20-point fourth quarter.
Jonathan Stewart added 109 yards rushing and a TD on 25 carries, snapping Minnesota's NFL-long steak of 36 games without allowing a 100-yard rusher.
It was that kind of thorough beating for the Vikings, which left Favre sitting alone on the bench in the final minutes.
"We were playing great defense until the fourth quarter," said Vikings defensive end Jared Allen, outplayed by Carolina counterpart Julius Peppers. "We've got to dig down, we've got to find that fight within us to win games. You've got to battle for it."
The Panthers (6-8) lost top rusher DeAngelo Williams to a first-quarter ankle injury, then made numerous key errors that kept them out of the end zone until an improbable touchdown early in the fourth quarter.
Facing third-and-26, Moore heaved a pass to the right side and Smith beat Antoine Winfield for a 42-yard touchdown and a 12-7 lead.
It was the beginning of three touchdowns on consecutive drives. Smith's 45-yard, tackle-breaking catch-and-run set up Stewart's 3-yard TD run.
Moore, looking poised in the pocket and getting time to throw despite an offensive line that lost both starting tackles, then threw a 2-yard TD pass to Stewart to put it away.
Favre's difficult night ended when he was picked off in the end zone by Chris Harris on the ensuing possession.
"That was one of our more complete games," Panthers coach John Fox said. "We had a more complete one out in Arizona, it seems like 100 years ago. But it was good to see those guys show up like they did tonight."
Minnesota lost for the second time in three games - both road routs on Sunday night - to drop to 4-3 away from home ahead of a visit to Chicago next Monday night.
It was about 35 minutes before kickoff when the video boards showed Pittsburgh's winning touchdown on the final play over Green Bay that clinched the NFC North title for Minnesota.
The Vikings fans in the stands - and there were plenty of them - cheered wildly. But there was little reaction from the players. Favre did stop briefly to check the replay, which showed Mike Wallace was inbounds on his diving catch as time expired for the Steelers. Favre then took a snap and fired the ball downfield to continue his warmups.
The Vikings' chance to clinch a first-round bye Sunday was dashed a few minutes earlier when Philadelphia beat San Francisco. But with the Saints' first loss, the Vikings had a chance to move within a game of the Saints for home-field advantage throughout the NFC playoffs.
Instead, Minnesota remains two games back thanks to a flat performance full of missed tackles and dropped passes.
With a sack and numerous hurries, Peppers led Carolina's impressive pass rush. Favre was sacked on each of his first two possessions, the second after slipping on the turf and leading to him changing to longer cleats.
The Panthers were officially eliminated from playoff contention after Dallas' win Saturday night, but they had more fire. Moore led Carolina on an 8-minute first-half drive that ended with his 1-yard touchdown pass to Brad Hoover early in the second quarter, the fullback's first receiving TD since 2004.
Ray Edwards blocked the extra point, John Kasay's first missed PAT since 2005 and ending his streak at 157.
The Vikings took the lead late in the second quarter on Peterson's spectacular 4-yard run. Seemingly stood up by Harris, Peterson spun away and broke Richard Marshall's tackle late in the second quarter to make it 7-6.
In a disappointing season full of injuries and lost opportunities, the Panthers had a 47-yard field goal taken off the board on the final play of the half after Garry Williams' false start.
Fox decided against letting Kasay try a 52-yarder, and Moore's desperation pass into the end zone was knocked down.
A later TD pass to Steve Smith was wiped out by a holding call, the kind of mistakes that would seemingly end the Panthers' hopes against a high-powered offense. But Minnesota didn't capitalize.
Favre was just 17 of 27 for 224 yards and no touchdowns. Peterson was held to 35 yards rushing, a similar poor performance that he had two weeks ago against Arizona.
"You're just disappointed with the loss," Minnesota linebacker Chad Greenway said. "It doesn't really matter how they did it. We just came down here and wanted to play a statement game and play your best football coming down the stretch and we couldn't do that."