Panthers vs. 49ers AI Picks: MNF Predictions & Best Bet for Monday Night Football Tonight

Two NFC playoff hopefuls face off tonight when the San Francisco 49ers (7-4) host the Carolina Panthers (6-5) on Monday Night Football (8:15 p.m. ET, ESPN), and our Panthers vs. 49ers AI predictions expect the home favorites win in blowout fashion at Levi's Stadium in Santa Clara, Calif.

We've trained the latest ChatGPT model to offer its exact score prediction and projected stat leaders for both teams, as well as its best MNF prop bet tonight. You can catch the rest of our (human) expert picks with our NFL Week 12 predictions.

🤖 Panthers vs. 49ers AI predictions: Monday Night Football

See all of our NFL AI predictions with projected scores for every game.

🔢 49ers projected stats

• Passing leader: Brock Purdy – 21/30, 248 yards, 2 TD, 0 INT
• Rushing leader: Christian McCaffrey – 17 rushes, 92 yards, 1 TD
• Receiving leader: Jauan Jennings – 5 receptions, 77 yards, 1 TD

🔢 Panthers projected stats

• Passing leader: Bryce Young – 20/34, 188 yards, 0 TD, 1 INT
• Rushing leader: Rico Dowdle – 14 rushes, 56 yards
• Receiving leader: Tetairoa McMillan – 6 receptions, 71 yards

🔮 Panthers vs. 49ers prediction

San Francisco enters Week 12 with a clear structural edge in both phases, and the matchup trends strongly toward its strengths. Brock Purdy’s efficiency in the quick and intermediate passing game forces Carolina into predictable zone looks, and Kyle Shanahan’s motion-heavy approach keeps linebackers in conflict. Expect Christian McCaffrey to be a consistent chain-mover against his former team, with the Panthers struggling to match San Francisco’s physicality at the point of attack.

The Panthers struggle to generate explosive plays, and Bryce Young’s development has been slowed by protection inconsistencies and a limited supporting cast. Star rookie receiver Tetairoa McMillan gives them some juice on the perimeter, but the 49ers’ defensive line disrupts timing before Carolina’s routes can develop. Sustained drives are difficult, red-zone efficiency is a major issue, and the 49ers’ ability to win early downs produces a controlled, methodical victory. The projection sees Carolina settling for field goals while San Francisco’s offense maintains a comfortable multi-score cushion.

Score prediction: 49ers 27, Panthers 9

💰 Best player prop bet for Monday Night Football

See all of our experts' NFL picks based on the latest NFL odds.

⬆️ Brock Purdy Under 36.5 yards longest completion

This matchup sets up well for Purdy to be efficient, not explosive, which makes the Under on his longest completion a strong value play. With San Francisco projected to control this game from the opening quarter, Kyle Shanahan is unlikely to dial up many deep shots. Purdy’s 2025 tape also supports this angle: his deep-attempt rate has dipped while Shanahan leans more heavily into rhythm throws, layered route concepts, and yards-after-catch opportunities rather than pure air-yard aggression.

The projected game script strengthens the Under even further. With the 49ers expected to lead comfortably through the second half, the offense should transition into a shorter, ball-control passing plan and increased carries for McCaffrey. That reduces Purdy’s chances of hitting a big downfield completion late. Even if San Francisco moves the ball efficiently, the Panthers tend to keep plays in front of them and force long drives.

Best bet: Brock Purdy Under 36.5 yards longest completion (-114 via FanDuel)

📺 How to watch Monday Night Football: Panthers vs. 49ers

• Date: Monday, Nov. 24
• Kickoff: 8:15 p.m. ET
• Location: Levi's Stadium (Santa Clara, Calif.)
• TV: ESPN

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