Carolina Panthers vs. San Francisco 49ers Prediction (November 24, 2025)
The Carolina Panthers and San Francisco 49ers offer an unexpectedly meaningful week 12 Monday Night Football showdown, where the Niners will be touchdown favorites.
Carolina has done well to rebound following a slow start, with the Panthers quietly winning five of their last seven games. San Francisco has battled injuries to stay competitive all year, and will hope to add to a solid 7-4 mark.
The 7-point spread indicates the Niners are the easy pick, but betting on the NFL is rarely so simple. That said, the game does have a robust 49.5 total, while the 49ers are getting healthy at the right time.
Are the 49ers a smash bet, or is there sneaky value with Carolina? I’ll inspect the latest odds and key matchups, working my way to this game’s best bets and my Panthers vs. 49ers prediction.
Game Info Snapshot
- Date & Location: Monday, November 24th, 2025 | Kickoff at 7:15 pm ET (ABC/ESPN) at Levi’s Stadium in Santa Clara, CA
- Team records entering the game:
- Panthers: 6-5
- 49ers: 7-4
- Odds (from ESPN Bet)
- Spread: Panthers +7 (EVEN) | 49ers -7 (-120)
- Moneyline: Panthers (+320) | 49ers (-425)
- Total: Over 49.5 (-110) | Under 49.5 (-110)
The Panthers vs. 49ers odds indicate San Francisco is the far better team. They only have one more win, but they are at home and are a lot healthier than they were even a couple of weeks ago.
The game total is fairly hefty, which is a credit to the 49ers offense, but also to both defenses not playing at an elite level on the year.
Storylines to Watch
The biggest Panthers vs. 49ers storyline has to be the fact that Carolina is 6-5 and has a shot at making the playoffs. The Panthers have big upsets over Dallas and Green Bay on the year, while they managed to sweep the Falcons.
Carolina could lose this game and still be in position to make a playoff run. Either way, they have enjoyed a better-than-expected 2025 campaign and should feel good about where they are now compared to a year ago.
There’s more to keep in mind for this game, so check out the following Panthers vs. 49ers storylines:
- Turning a Corner?: Bryce Young went off last week (448 passing yards, 3 TDs). Is this a sign of things to come? If so, he could put on a show under the bright lights of MNF.
- C-Mac Revenge: Christian McCaffrey is probably thankful the Panthers traded him to the 49ers, but there’s likely something about this matchup that will give him some added motivation to perform well.
- Full Strength: San Francisco is still down key bodies on defense, but the offense is rounding into form. George Kittle, Ricky Pearsall, and Brock Purdy have missed a lot of action this year, but all three will be available against Carolina.
Team Profiles
Carolina Panthers
The Panthers did not look like a playoff contender to start the year, as they got housed 26-10 by the Jaguars in week one and then got tripped up by Arizona in week two.
Carolina came to life after that, as they’re a rock-solid 6-3 ever since. They haven’t been the most consistent bunch, but they have exhibited a competent offense and a defense that has flashed the ability to dominate.
Following a win over Atlanta last week, they are presently in position to make a play for first place in the NFC South.
Here’s a look at where they’ve stood out the most so far:
- Pound the Rock: The Panthers are a run-first team, and they’re good at it. They enter this MNF matchup ranked 12th in rush rate and generate 127.1 rushing yards per game (9th in the NFL).
- Smart Play: Carolina is a fairly young team that is learning on the fly how to win games, but one thing they don’t do is commit a lot of mental errors. The Panthers come into this game ranked 2nd in penalties per game and 3rd in penalty yards per game.
- Bend, Don’t Break: Carolina’s defense isn’t consistently dominant at much, but they tend to stifle teams inside the 20. They let you drive the ball regularly, but they’re only allowed a score 52% of the time inside the RZ (9th best).
San Francisco 49ers
The 49ers have to feel pretty good about their 7-4 start when you consider the injuries that have struck their roster. Quarterback Brock Purdy has only suited up for three games, while key contributors like George Kittle and Ricky Pearsall have missed a lot of action.
San Francisco is getting healthy on offense, though, and that could help mitigate some issues they have dealt with on the defensive side of the ball.
Overall, this is still a well-coached and talented group that is at least average in most regards on both sides of the ball.
Here’s a quick look at what they’ve excelled at in 2025:
- Finish the Job: This has not been a very cohesive offense, but they’ve still done a good job moving the ball and finishing drives. On the year, they convert 62% of the time inside the 20, which is good for 11th in the NFL.
- Pass Happy: San Francisco’s ground game has not been very good, which has them passing out of necessity. They own the league’s 13th-highest pass rate, but they’ve also simply been very good in that department, ranking 7th in completion rate, 8th in yards per pass, and 2nd in passing yards per game.
- Stiff Front: San Francisco hasn’t run the ball very well, but they’ve at least been stingy on the ground defensively. They come into this matchup ranked 12th against the run and are allowing just 4.1 yards per carry (13th).
Key Matchups & Angles
Check out the key Panthers vs. 49ers vs. matchups:
- Panthers rush offense vs. 49ers run defense: This is easily the key to this game. Carolina typically needs to run well to stay in games, so it’ll be their strong rush offense against a solid defensive line for the Niners.
- Christian McCaffrey vs. Carolina’s defense: The 49ers will also want to try to get their best offensive weapon going. It’s a solid spot to try, as Carolina is just 17th against the run. Just as importantly, McCaffrey is extremely active as a receiver out of the backfield, and the Panthers allow the 4th most catches (54) to RBs.
- George Kittle vs. Carolina’s defense: Kittle hasn’t played much this year, and the 49ers could opt to have him block a lot, but he also could smash here. On the season, the Panthers have been torched by tight ends to the tune of 718 yards (4th most).
Betting Trends & Odds Context
Take a look at the latest 49ers vs. Panthers odds (from ESPN Bet):
| Team | Spread | Moneyline | Total |
|---|---|---|---|
Panthers | +7 (EVEN) | +320 | Over 49.5 (-110) |
49ers | -7 (-120) | -425 | Under 49.5 (-110) |
Take a look at some key betting trends for this showdown:
- Public Betting: The public doesn’t like Carolina’s chances here, as 96% of the bets favor San Francisco, and they’re getting 96% of the money, too.
- Record History: These teams have only played each other 23 times, with Carolina surprisingly holding a narrow 13-10 edge. It’s been all 49ers lately, though, as they won the last two meetings and three of the last five.
- ATS Tidbits: Carolina has been good (7-4) against the spread overall, while they are 4-2 ATS as the road team and 6-3 ATS as the underdog. The 49ers are 6-5 against the spread as a whole, and they are 4-2 ATS when favored.
Best Bets for Panthers vs. 49ers
Pick 1: Panthers ATS +7 (EVEN) – 7/10 Confidence
Why We Like It
Carolina isn’t an elite team, but neither are the 49ers at the moment. If they can pound the rock and avoid mental mistakes – two things they’ve proven they can accomplish – they can hang tight and make the Niners sweat this one out.
Risks/What to Watch
The 49ers are getting healthy, they’re at home, and they’re probably the better team overall. If they come out firing on all cylinders, they absolutely could tee off and dominate Carolina.
Pick 2: Under 49.5 (-110) – 7/10 Confidence
Why We Like It
There is plenty of offensive upside in this game, but the Panthers could dictate the pace on the ground. If they can do that, this will be a slower and low-scoring affair.
Risks/What to Watch
San Francisco has the leg up in several of these matchups. If they take advantage of them and put points on the board early, we could be looking at a shootout.
Pick 3: Prop Play – George Kittle Over 50+ Receiving Yards (-152) – 7/10 Confidence
Why We Like It
Carolina does not stay in front of tight ends very well. On MNF, they have to track one of the best in the business. Kittle hasn’t been around much this year, but he’s the type of guy who feasts in favorable spots. A Kittle Anytime TD also looks great.
Risks/What to Watch
Player prop bets are inherently volatile, and it’s always possible the Panthers make a concerted effort to not let Kittle beat them. There’s always a chance the 49ers find success on the ground and simply utilize Kittle more for his blocking prowess.
As Panthers vs. 49ers lines shift throughout the week, staying updated matters—track every odds change and compare football betting options at our top football betting sites.
Final Verdict: Panthers Make the 49ers Sweat on MNF
My 49ers vs. Panthers prediction is that we get a game that isn’t settled until very late, possibly by a field goal.
Both of these teams want to run, and both teams have a lot of experience in tight games. The high total suggests we could get into a shootout, but my guess is the Panthers score first and milk the clock a bit, opting to control time of possession and limit the 49ers’ offensive opportunities.
That should help us hit the Under, but the 49ers have superior coaching, better talent, and are at home, so a late rally and field goal should get them the win in the clutch.
Final Score Prediction: 49ers 23, Panthers 20
