Carolina Panthers vs San Francisco 49ers Prediction, Odds & Expert Picks for Monday Night Football in NFL Week 12 for Monday, 11/24/25

Markets and NFL media heads are high on the Panthers after they did something highly unusual: win a big game on the road with Bryce Young under center. Even more unusual was Young’s form. The former Alabama star made Panthers’ history last Sunday, throwing for a franchise game-high 448 yards and three touchdowns in a winning effort at Atlanta. Down 21-10 at halftime, at one point Young had to exit to Carolina’s locker room to address a new ankle injury. Immediately it felt like the same old story; an ailing group under new coach Dave Canales, who can’t quite get it right. The Panthers’ offense caught fire, along with their defense permitting just 92 yards and six second half points, and history will see Week 11 as an impressive comeback win for Canales’ group, a roster that’s proving it’s not built the same as previous iterations.

Unfortunately, we’re here to spoil the party. While the Panthers win was impressive, we must consider their opponent. After starting the season looking like a formidable NFC contender, the Falcons loss on Sunday was their fifth in a row. Even worse, Michael Penix Jr., their second-year starter who took over for Kirk Cousins last season, left with what’s likely a season-ending knee injury. Atlanta’s defense has also been floundering for over a month. 

This Sunday Carolina will face a much bigger road challenge. The 49ers are coming off an inspiring victory on Sunday, one that left their fans hopeful that this season may have a higher ceiling than once thought. San Francisco leveraged three Arizona turnovers, but with Brock Purdy back their offense was smooth and explosive, turning five red-zone possessions into four touchdowns. They clobbered their rivals 41-22 on their enemy’s home field, and perhaps most importantly: Purdy looked fantastic (19-26, 200 yards, 7.7 yards per pass, three touchdowns). It was the kind of win that catalyzes future success.

The Panthers deserve a ton of credit for their turnaround this season, but the 49ers still have championship fabric throughout their roster, including a coach and quarterback pairing that’s as effective as any in the NFL. The Niners’ offense is also healthier than it’s been all season, with Jauan Jennings, Ricky Pearsall, and George Kittle all ready to roll for Week 12. We like the home team to pull away.

Panthers vs 49ers best bet: 49ers -6.5 (-115) available at time of publishing. Playable to 7.

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