Will Carolina Panthers beat San Francisco 49ers? Our predictions, bets to know
AI-generated summary reviewed by our newsroom.
- Panthers on the road vs. San Francisco 49ers on “Monday Night Football” (8:15 pm kickoff).
- Matchup will be first time since McCaffrey trade of 2022 that CMC has faced Panthers.
- In game predictions, Charlotte Observer staff is split on the 49ers-Panthers outcome.
For the first time all season, the Panthers are playing after the sun has gone down.
And that’s not the only first they will soon experience, either.
The Carolina Panthers (6-5) will face the San Francisco 49ers (7-4) in Levi’s Stadium on Monday Night Football on ESPN (and locally in Charlotte on WBTV-Channel 3). Kickoff is set for 8:15 p.m. ET. It’ll mark the first time the teams have played since Oct. 9, 2022 — in other words, the first time since former Carolina superstar Christian McCaffrey was traded to San Francisco.
And while the McCaffrey-versus-his-old-team trope will be an important subplot Monday, another will come to the fore as well. And that’s this:
It could be a good game.
The Panthers are fresh off the kind of win they needed, against the Atlanta Falcons. That 30-27 thriller featured quarterback Bryce Young having the game of his NFL life to date — piling on a franchise-record 448 passing yards and an NFC Offensive Player of the Week nod and a 10th career game-winning drive that sealed the overtime win. The Panthers have now seemingly played in every game imaginable: a blowout win, a few blowout losses, one close loss and several close wins. It has delivered them consequential football in November.
The 49ers, similarly, had a refreshingly great week in Week 11. The 41-22 win over the Cardinals featured the triumphant return of Brock Purdy. The quarterback had missed most of the season because of a big toe injury, but came out soaring against the Cardinals to the tune of 19 of 26 for 200 yards and three touchdowns for a passer rating of 133.5. The defense did give up a massive day to Cardinals QB Jacoby Brissett — and according to Team Rankings is particularly vulnerable as a pass defense — but still, the 49ers are a worthy opponent for just about anyone this season.
So who will win?
The Charlotte Observer has asked reporters Mike Kaye and Alex Zietlow, as well as columnist Scott Fowler, to answer that very question. Everything else you should know ahead of the game — including betting props to consider and broadcast information — can be found here, too.
Panthers-49ers inactives
Here are the Carolina Panthers inactives for Monday: WR Hunter Renfrow, LB Trevin Wallace, LB Christian Rozeboom, C Cade Mays, DT Jared Harrison-Hunte, TE James Mitchell, DT Cam Jackson.
The 49ers’ inactive list: RB Jordan James, WR Jordan Watkins, OL Connor Colby, DL Robert Beal Jr., DL Kevin Givens, LB Tatum Bethune, K Eddy Pineiro.
TV and radio channels for Carolina Panthers vs. San Francisco 49ers game
The Panthers-49ers will face off on ESPN’s Monday Night Football, with Joe Buck (play by play), Troy Aikman (analyst), Laura Rutledge (sideline reporter) and Lisa Salters (sideline reporter) on the call. Kickoff is at 8:15 p.m. ET, with coverage beginning slightly before then. You can also view the game on WBTV in Charlotte.
The game will also air on the radio on WRFX The Fox. That’s 99.7 FM in Charlotte; check out the Carolina Panthers Radio Network for local listings.
Other ways to listen on radio: National Radio on Westwood One (Ryan Radtke and Ryan Fitzpatrick) and Spanish radio on WXNC 97.3 FM / 1060AM (Jaime Moreno and Antonio Ramos).
Another fun programming note: Panthers legend Jake Delhomme will join the “Manningcast” with Peyton and Eli Manning on ESPN2. Others in the lineup, via Omaha Productions: Jerry Rice, Luke Combs, Colin Jost and Michael Che.
Betting information to consider
The Panthers, unsurprisingly, are 7.5-point underdogs in this road matchup, according to FanDuel Sportsbook as of Sunday. Taking the Panthers moneyline would yield a payout of +320; 49ers moneyline is -420. The over/under on the contest is 49.5 total points.
The Panthers are 7-4 against the spread this season. The 49ers, meanwhile, are 6-5 against the spread.
Some other bets you might find interesting:
- Player Passing Yards — Bryce Young. FanDuel has the line set at 204.5 passing yards for Young. And that might appear low considering the third-year quarterback’s huge day against the Falcons. But remember, Young has only thrown for over 200 yards twice now all season. It’s worth thinking a moment to mull this one over.
- Carolina Panthers — First Drive Result. This one is always fun. It’s a +300 payout for a Panthers offensive touchdown on the first drive; +340 for a field goal attempt; +105 for a punt; and +500 for “any other.” For what it’s worth, the Panthers have notched game-opening touchdown drives in each of their last two games.
- Anytime Third Quarter TD Scorer — Christian McCaffrey. Betting on McCaffrey this week will be rough because the sportsbooks don’t give great payouts for anything McCaffrey-related. He’s just that good. The best we could find is McCaffrey scoring a third-quarter touchdown at +250. Strange. But not getting in on any of the McCaffrey hullabaloo seems like a missed opportunity.
Game predictions: Panthers or 49ers?
In a not-so-stunning turn of events, Scott Fowler was the only one to correctly predict that the Panthers would turn around their fortunes against the Falcons. The correct pick puts him at 7-4 on the year, with Mike Kaye and Alex Zietlow haplessly stuck at 3-8. Check out our predictions this week below.
Fowler: 49ers 30, Panthers 20. As well as the Panthers are (sometimes) playing, they haven’t faced a running back playing as well as McCaffrey is this season. Three years after the infamous McCaffrey trade, the chickens come home to roost for Carolina. Put me down for McCaffrey scoring twice and leading the 49ers to an MNF win.
Kaye: 49ers 24, Panthers 23. San Francisco is banged up, but the return of Brock Purdy last week should settle things down a bit. The 49ers are struggling mightily against tight ends this season, but so are the Panthers. This does feel like a bit of a tossup, so I’ll go with the more proven QB and head coach at home in prime time, even if by a sliver.
Zietlow: Panthers 31, 49ers 28. The Panthers have only lost one one-score game in 2025. And even that deserves an asterisk, considering it wasn’t your typical close game; it featured a furious Panthers comeback attempt enabled by some late-game turnover magic and an onside kick recovery. My point: I predict this will be a close game, and with the Panthers’ passing offense rolling and the 49ers’ passing defense struggling, I think Carolina has the edge. Let’s dream a little bit, shall we?
This story was originally published November 24, 2025 at 5:00 AM.
