NFL Week 12 wraps up with a Monday Night Football matchup between the Carolina Panthers and San Francisco 49ers. It’s a vital NFC matchup for both teams as they look to remain in Wild Card contention. The Panthers delivered a huge victory over the Falcons last week with Bryce Young setting franchise records, while the 49ers bludgeoned the Cardinals as they begin to look like more of a force now they'[re getting healthy. Panthers vs 49ers on MNF kicks off at 8:15 pm ET live on ESPN, and here at Pickswise, we have everything you need to bet on this game! You can find out our NFL picks on the side and total, along with our experts’ best NFL player prop bets and Same Game Parlay picks. Let’s get into our Panthers vs 49ers picks and MNF predictions.
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NFL MNF picks & Panthers vs 49ers predictions
Chris Farley’s Panthers vs 49ers best bet: 49ers -7.5 (-102)
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 3 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 6 second-half points. 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 3 Arizona turnovers, but with Brock Purdy back the offense was smooth and explosive — turning 5 red-zone possessions into 4 touchdowns. The Niners clobbered their rivals 41-22 on their enemy’s home field, and — perhaps most importantly — Purdy looked fantastic (19-for-26, 200 yards, 7.7 yards per pass, 3 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 who are 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. I like the home team to pull away.
Chris Farley’s Panthers vs 49ers prediction: Over 49.5 (-110)
We should start by stating the obvious: no NFL team has more overs this season than the San Francisco 49ers. They are 7-3-1 to the over through 11 weeks. Of course, part of that is because of their litany of defensive injuries. Entering Week 12, they have 6 defensive players on injured reserve — including their 2 best players, Nick Bosa and Fred Warner. Because of those injuries they have consistently allowed points (22.9), but their offense is a big part of it, too. Whether it was Brock Purdy or Mac Jones, their offense continues to be productive. After all, it is run by Kyle Shanahan — widely regarded as one of the NFL’s best playcallers. The Niners have gained 349.4 yards per game, a top-10 mark, and now that their playmakers are healthy their average points are bound to rise (currently 23.7 per game, 15th).
The Panthers’ offense is unlikely to perform as well as they did this past Sunday (30 points, 486 yards), but they can still do some damage on Sunday. The Niners’ defense simply hasn’t been very good regardless of who has been on the field. According to advanced EPA metrics, they are 31st in defensive success rate and 26th in EPA per play. They have also allowed 114 points in their past 4 games. I don’t necessarily expect Bryce Young to have a repeat performance in the Bay Area this Sunday, but the Niners’ secondary is a bottom-5 program in EPA per pass. Plus, Young’s Week 11 showing should only produce more confidence. They can surely get into the 20s.
Find out all of our expert Panthers vs 49ers picks for MNF. Our experts are up +11.3 units this season!
Panthers vs 49ers player prop bets
Prop Holliday’s best MNF player prop bet: Ricky Pearsall (SF) over 3.5 receptions (+114)
After missing 6 straight games, Ricky Pearsall returned in Week 11 to the tune of 0 receiving yards on 2 targets and 1 reception. After the game, social media was quick to find several snaps where Pearsall was wide open and even had an easy TD look had Purdy seen him. These are the types of things that shake out in the film room and find their way into the following week’s game plan. For Week 12, Pearsall is playing a Panthers defense ranked 1st in zone coverage, where he’s seen 21 of his 30 targets for the season. Prior to his injury earlier this year, he was averaging 8 targets for 5 receptions a game. I believe this line is an overreaction and will be closer to -110 by kickoff.
See our best MNF player prop bets for Panthers vs 49ers
JutPicks’ Panthers vs 49ers TD scorer prediction: Ricky Pearsall (SF) anytime touchdown scorer (+230)
Considering he hadn’t played since Week 4, Ricky Pearsall looked awfully comfortable in the 49ers’ Week 11 blowout win against the Cardinals. He played 75% of the snaps, while Brock Purdy left plenty of opportunities on the table to target Pearsall, who was open on multiple occasions, including a red-zone opportunity. Even in a crowded offense that features Christian McCaffrey and George Kittle, Pearsall is a fine bet at +230 odds to score a TD on MNF.
JutPicks’ Panthers vs 49ers touchdown scorer pick: Brian Robinson Jr. (SF) anytime touchdown scorer (+475)
Let’s take a shot on Brian Robinson Jr. to find the end zone, who is the backup running back for the 49ers. Robinson has been given the keys to get more work as the season has progressed. He ran the ball 8 times last week, with half those carries coming in the 4th quarter. Though those carries came with the 49ers up 3 possessions, San Francisco has not shied away from going to Robinson more frequently. At +475 odds to score a TD with BetMGM, that’s enough value to throw some change on Robinson to get garbage-time work in a game the 49ers should have full control of.
After a +525 winner on TNF, get JutPicks’ full analysis for his Panthers vs 49ers touchdown scorer best bets for MNF
Carolina Panthers vs San Francisco 49ers Same Game Parlay
After cashing our last 2 MNF SGPs at +753 and +750 odds, don’t miss our Panthers vs 49ers Same Game Parlay as we look to make it 3 in a row!
Over 49.5 (-110)
Brock Purdy returned from his latest injury in Week 11 and looked great, leading San Francisco to a 41-22 rout of Arizona. Purdy completed 19 of 26 passes for 200 yards and three touchdowns. More success should be in store for an offense that is healthier than it has been all season long. Tight end George Kittle is back in action along with receivers Ricky Pearsall and Jauan Jennings. Unfortunately for the 49ers’ defense, it is a banged-up unit that is without Nick Bosa and Fred Warner for the rest of the year. By EPA metrics, the Niners are #31 league wide in defensive success rate. They have given up 114 points over their past 4 contests. The Panthers’ offense may not be anything special, but they should be playing with some confidence following last weekend’s stellar performance against the Falcons.
Bryce Young to record 250+ passing yards (+240)
If only Young could face the Falcons every game… The former #1 overall pick torched Atlanta for 448 yards and 3 touchdowns during last week’s 30-27 overtime victory. That was preceded by a 251-yard, 3-touchdown effort in the 2024 finale against the same opponent. It’s worth noting that the Falcons were the #1 passing defense in the entire league heading into last week, so Young should also be able to find success against other teams. That includes the 49ers, who are second-to-last in passing defense at 254.5 yards per game allowed. They are giving up the eighth-most yards per attempt (7.6). As a considerable underdog, Carolina will likely be playing from behind early and often – resulting in a whole lot of passes thrown by Young.
Christian McCaffrey to record 50+ receiving yards (+120)
McCaffrey is the best pass-catching running back in the NFL. The Stanford product has already hauled in 74 passes on 96 targets for 732 yards and 5 touchdowns this season. He did not really miss a beat with Mac Jones under center, but his rapport with Purdy is even better. In the 3 games started by Purdy this year, McCaffrey is averaging 67 receiving yards and he has found the endzone twice via the air. Another productive outing should be in the cards against Carolina. The Panthers have allowed the fourth-most receptions to opposing RBs in 2025. Count on McCaffrey victimizing his former team to a significant extent on Monday Night Football.
Panthers vs 49ers Parlay odds: +750
NFL Week 13 predictions
Get set for next week’s NFL action with our expert’s NFL Week 13 opening lines analysis, along with their best bet to lock in right now before the odds change!
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