NFL Monday Night Football Best Bets: Panthers vs 49ers

Playoff races are coming into focus as we head into the stretch drive of the 2025 NFL season. The San Francisco 49ers and Carolina Panthers need a win to stay in their respective division races, while also staying in the postseason conversation. That amplifies the stakes of this Monday Night Football battle, with the victor earning the leg up in the standings.

We’ve got you covered for betting purposes, highlighting our MNF best bets!

Where to Watch Carolina Panthers vs San Francisco 49ers

Stadium: Levi’s Stadium
Location: Santa Clara, CA
Where to Watch: ESPN/ABC
Time: 8:15 p.m. ET
Spread: SF -7.5 (-102) | Total: 49.5 (-110/-110)
Moneyline: SF -420 | CAR +320

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Over the past few weeks, we’ve seen a resurgent San Francisco 49ers squad. Most of their top playmakers have finally returned to full health, which has precipitated a massive spike in offensive efficiency. Still, that surge in scoring has come without a corresponding increase in production, implying the 49ers are regression candidates in the short term. That benefits the Panthers on Monday Night Football.

San Francisco’s recent scoring surge is built on unsustainable metrics. Over their last three games, the Niners are up to 33.7 points per game, recording no fewer than 26 points in any one of those contests. However, that increased output is contraindicated in their 351.3 yards per game, which is actually a decrease compared to their season-long average of 361.8. More plainly, the 49ers are scoring more points while putting up fewer yards. Regression is coming for the 49ers.

Consistency has limited the Panthers’ ceiling, but they have a chance to make a big move up the standings. The Buccaneers were easily defeated on Sunday Night Football, meaning the Panthers will take over the NFC South lead with a win over the 49ers. If their last performance was any indication, the Panthers are ready to make that leap. They put up 486 yards of total offense last time out, which was the third time in seven games in which they surpassed the 400-yard plateau.

Carolina will have the chance to give the 49ers a taste of their own medicine at Levi’s Stadium. San Francisco’s increased scoring capacity is contraindicated in its underlying metrics. Conversely, the Panthers are on the verge of a breakout, validated by their recent increase in production. That tilts the gambling balances in Carolina’s favor, setting the Panthers up to cover the spread on Monday Night Football.

Best Bet: Panthers +7.5 -120

Christian McCaffrey has re-emerged as the top 49ers’ playmaker. A tepid start to the campaign has long since been forgotten, and McCaffrey’s recent form proves that he’s still the offensive catalyst the Niners need him to be. We’re betting he shows his full arsenal against the Panthers tonight.

Over the past month, McCaffrey has put together his best performances of the season. Since Week 7, the two-time All-Pro has totaled 371 rushing yards on 85 carries, yielding 4.4 yards per carry. On a more absolute basis, the Niners’ running back has eclipsed 80 rushing yards in three of those five contests, including a season-best 129 rushing yards at home back in Week 7.

Triple digits might be out of the question, but McCaffrey should have no problem reaching the 80-yard threshold against the Panthers. Carolina sits in the middle of the pack, giving up 113.1 rushing yards per game, but that total has been on the rise more recently. Three of their last four opponents have rushed for 122 yards or more, resulting in a hefty 149.0-yard average across the four-game sample.

McCaffrey has taken a front seat in game-planning, and he will be called upon frequently as the 49ers try to expose the Panthers’ most notable weakness. In the end, we’re forecasting another robust performance from the 49ers’ bell cow, backing McCaffrey to eclipse 80 rushing yards on Monday Night Football.

Best Bet: Christian McCaffrey to Record 80+ Rushing Yards +126

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