The Carolina Panthers (6-5) will head to Levi’s Stadium on Monday to face the San Francisco 49ers (7-4). San Francisco is laying points as the home favorite, but both of these teams are in playoff contention and will be eager to make a statement here. Before kickoff in this Monday Night Football matchup, continue reading to get my Panthers vs 49ers prediction below.
Our Panthers vs 49ers Pick
Pick: Panthers +7
Confidence: 3/5
Game Snapshot
- Matchup: Carolina Panthers at San Francisco 49ers
- Date & Time: Monday, November 24, 2025, 8:15 PM ET
- Venue: Levi’s Stadium, Santa Clara, CA
- Broadcast: ESPN
Key Storylines
The Carolina Panthers have made headlines this season by going from one of the worst teams in the NFL to being a playoff contender. Carolina got an overtime win over the Atlanta Falcons last week to move to 6-5 on the season. They are just a half-game behind the Tampa Bay Buccaneers for first place in the NFC South going into this week. A win could put the Panthers in first place by the time Week 12 concludes.
San Francisco is also trailing in their division, sitting behind the Seattle Seahawks and Los Angeles Rams in the NFC West standings. The Niners appear to be in a good place to end up with a Wild Card spot in the NFC. But they can’t afford to lose games like this one at home if they want to remain in a comfortable spot in the playoff chase.
Special teams will be a big storyline on the Niners’ side of this game. Matt Gay has been signed by San Francisco after Eddy Piniero suffered a hamstring injury. How Gay performs right away if he is called into action will be important for the home team.
Quarterback Play
Carolina – Bryce Young: Young is in his third season with the Panthers. He has struggled at times in 2025 but remains capable of electric performances. He has thrown for 1,962 yards with 14 touchdowns and 7 interceptions. Young needs to simply avoid turning the ball over, allowing the Panthers’ highly effective running game to lead the way.
San Francisco – Brock Purdy: The 49ers quarterback is back on the field after missing some time due to injury. Mac Jones is leading the Niners in most major passing stats this year. But the Niners are better with Purdy on the field for the most part.
Betting Trends
- Carolina is 7-4 against the spread so far this season.
- San Francisco is 6-5 against the spread going into this contest.
- The Niners have gone 7-3-1 to the over through their first 11 games of this year.
- Carolina is 6-5 to the over entering Week 12.
Panthers vs 49ers Model Projection
Projected Score: Panthers 20 – 26 49ers
Win Probability: Panthers 28%, 49ers 72%
Final Thoughts
The 49ers should get a win at home here that will be huge for their playoff hopes. But I’m going to take the points with the Carolina Panthers in this game. Special teams uncertainty for the Niners could impact their ability to win with margin, as could the poise of Bryce Young.
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