SAN FRANCISCO -- The Carolina Panthers can now say they have that signature win everybody has been waiting to see: on the road, against the reigning NFC champions, in November.
While facing one of the NFL's brightest young quarterbacks, to boot.
Carolina's swarming, opportunistic defense stopped Colin Kaepernick in his tracks.
Drayton Florence intercepted a pass by Kaepernick in the final minute to seal a 10-9 victory Sunday to snap the San Francisco 49ers' five-game winning streak and give the Panthers their fifth straight win.
So much for the idea that Carolina hadn't beaten any team of consequence thus far.
"I don't think it really bothers us, it gives us the opportunity to step up to the challenge. We did," said wide receiver Steve Smith, who had six receptions. "A win like this can boost us, a win like this can continue to give us life throughout the season, and make us feel like we're working for something, and we are."
Graham Gano kicked a 53-yard field goal with 10:05 remaining that held up as the Panthers (6-3) twice shut down Kaepernick on last-ditch drives with swarming defense.
DeAngelo Williams broke two tackles for a 27-yard touchdown run late in the first half that pulled Carolina within 9-7. Gano missed wide left on a 48-yard field goal in the third period, but came through later.
San Francisco (6-3) got the ball back with 5:25 left at its 1, then again with 1:02 to go.
This was hardly the highly touted showdown between 2011 No. 1 overall pick Newton and Kaepernick, the sixth quarterback drafted that year, in the second round. They roomed together during the scouting combine.
For Newton, the numbers hardly mattered.
"This game is a maturity jump for us, because in the past what I've been a part of, we've been somewhat uncertain of how we will turn out in these types of games," Newton said. "We needed that type of game, just to be in a dog fight, in somewhat of a barnburner, to show what type of team this really is."
Kaepernick went 11 for 22 for 91 yards with an interception and was sacked six times for a 42.0 passer rating. Newton was only slightly better, going 16 of 32 for 169 yards, an interception and four sacks for a 52.7 rating.
For two teams that have been putting up points at a prolific pace for the past month, the defenses dictated this one.
"As the game went on, it got more and more intense," Smith said.
More than losing the game, the 49ers' losses of Davis and Reid could be troublesome for the reigning NFC champions as they hit the road next week for New Orleans, then go to Washington.
"We'll do what we do, bounce back, regroup, refit and reorganize and come back this week," coach Jim Harbaugh said.
Davis didn't return after sustaining a concussion in the second quarter, then Reid went down on a helmet-to-helmet hit on Tolbert in the third. Earlier, Reid recovered a fumble to give him five takeaways in an already-stellar rookie season that also includes three interceptions.
Frank Gore had 16 carries for 82 yards, accounting for most of San Francisco's 151 total yards.
"For the most part, I don't really think they did anything that necessarily confused us," 49ers center Jonathan Goodwin said. "They only gave up nine points. It's hard not to give them credit. We expected it to be a physical game. Did we expect to only score nine points? Nah."
Dawson put San Francisco ahead on a 52-yard field goal on the team's opening drive, then kicked second-quarter field goals of 43 and 25 yards.
But Kaepernick could never get his team in the end zone in its first game since a bye on the heels of a win over Jacksonville in London.
49ers pass-rushing specialist and 2012 All-Pro linebacker Aldon Smith played limited snaps after missing five games to undergo treatment for substance abuse.
Wide receiver Mario Manningham started and had three catches in his season debut, nearly 11 months after a serious left knee injury that required surgery.
Carolina got going after managing only minus-7 yards passing and 12 total yards in the first quarter. The Panthers finished with 250 total yards.
"This one really did come down to the way the defense played," Panthers coach Ron Rivera said. "Any time you put yourself in a position where you can force the other team to kick field goals, you get a chance to win."
The 49ers also lost TE Garrett Celek to a hamstring injury in the first quarter, while DT Ray McDonald hurt an ankle. ... Panthers LB Chase Blackburn did not return in the second half because of a foot injury.
Matt Hasselbeck will start at quarterback for the Indianapolis Colts on Thursday night when they visit the Houston Texans, according to a league source.
Cowboys owner Jerry Jones was a little taken aback Wednesday when informed of linebacker Greg Hardy's curious choice of words to describe his return.
Dolphins starting quarterback Ryan Tannehill admitted Wednesday that he made disparaging remarks to his scout-team defense during last weekend's practice in London.
Giants wide receiver Odell Beckham Jr. said he doesn't believe he should have been fined $8,681 for his actions in Sunday's victory in Buffalo, and he plans to appeal the fine.
Amid fans' growing restlessness with him as the 49ers' quarterback, Colin Kaepernick said Wednesday that he doesn't play for "job security."
Adam Jones told ESPN Radio's Dan Le Betard Show on Wednesday that a phone call from Cincinnati Bengals coach Marvin Lewis nearly six years ago saved his life.