49ers vs. Panthers Monday Night Football odds, predictions: Best bets, player props

While the 49ers always come with expectations, those with a stake on Monday Night Football being an interesting matchup each week had to see a late-November game with the Panthers traveling to San Francisco, and say, “Wait … what?”

Sure enough, because the NFL is the master of the unpredictable, Carolina is a surprising 6-5 and thoroughly in the mix for NFC South. While the division seems like an outside shot for the Panthers (given they’re still +600) and the only route to the playoffs, a win over the 49ers (7-4) would create a tie with San Francisco in the standings.

Yes, Panthers-49ers is a high-leverage game, and whoever wins should also see their head coach get some buzz for Coach of the Year (with Dave Canales at 35-1 and Kyle Shanahan 25-1).

As far as which team gets the boost from this game, what is predictable is that the betting market is leaning toward the less-surprising squad. Last Sunday’s opening line of -6.5 quickly moved up to -7, and tipped across the key number to -7.5. Bettors are charged with figuring out why, and whether the side is even the best look for Monday night.

Odds courtesy of BetMGM.

Carolina Panthers at San Francisco 49ers (-7.5, 49.5)

Despite suffering an assortment of injuries that would have broken a team with a weaker infrastructure, the 49ers have an impressive 7-4 record. Shanahan’s group has stayed afloat in time for the necessary players to return, but only on the offensive side of the ball.

George Kittle, Ricky Pearsall and, most importantly, Brock Purdy, have returned to bolster an offense that was being carried by Christian McCaffrey (among the leaders in receiving yards this season). Without Fred Warner, Nick Bosa and first-round pick Mykel Williams for the rest of the season, the Niners’ offense knows going in that they’ll have to outscore every opponent.

Carolina’s defense started out the season struggling against the pass, but has gotten to a point where it is above average, thanks to a misleading stretch in Weeks 7-11 where it has had a top-10 defensive success rate on opponent dropbacks. In Week 7, the Panthers were gashed by the Bills’ James Cook on the ground, so the Bills didn’t need to throw much in a blowout win. Two weeks later, Carolina gave up one big play too many against Tyler Shough. Before he was knocked out of the game last week, Michael Penix was 13-of-16 for 175 yards.

The Panthers are up to 15th in overall EPA/play (adjusted for turnovers and garbage time), three spots ahead of the 49ers. Even before San Francisco lost Warner, the 49ers were a middle-of-the-pack defense in EPA/play and Success Rate. Since losing Warner early in Week 6, the 49ers’ defense is 23rd in overall EPA/play allowed, and 28th in rushing success rate allowed.

These two are among the four teams that still haven’t had their bye yet, waiting for Week 14 for a rest, which suggests mediocre defensive units lacking depth could be getting tired.

Carolina is facing an offense that’s whole, with Purdy willing and able to push the ball down the field. The Panthers, though inconsistent, have shown they can score against weak defenses – getting 30 against the Falcons and Cowboys, and 27 against the Dolphins.

Look for the 49ers to stretch out an early lead, pushing 30 points, with the Panthers able to stay within striking distance, creeping this one over the total.

Bet: Over 49.5 total points

Rico Dowdle under 75.5 rushing yards (-115)

Dowdle’s emergence, with a pair of massive games against the Dolphins and his former team — the Cowboys – followed by a workhorse-effort in the Panthers’ upset of the Packers, gave him the starter’s role in Carolina. However, since he was attended-to with a leg injury in Green Bay, Dowdle has 37 carries for just 98 yards in back-to-back games.

The 49ers’ defensive injuries have hurt their pass defense, with Bosa not there to rush on passing downs, and Warner no longer patrolling the middle of the field, but San Francisco rotates six different players listed as defensive tackles, allowing the Niners to stay big and fresh against the run.

Ricky Pearsall over 41.5 receiving yards (-115)

Along with Purdy, Pearsall made it through his return last week unscathed, not exactly easing his way back with a 75% snap rate in a game that was a blowout in the fourth quarter. Without an injury designation this week, we can expect Pearsall to be at full speed, which makes him a prime candidate to get schemed open down the field, as well as getting frequent looks as one of Purdy’s favorite targets going back to the end of last season.

Christian McCaffrey under 124.5 rushing + receiving yards (-115)

Calling McCaffrey a horse instead of an old work-truck is complimentary to his speed, but given what the 49ers have had to put him through — 30-plus touches in four of their last six games – if the Niners can save some mileage on their star runner, they probably should leave him in the garage when possible.

Now that Purdy is back, he can distribute to Pearsall, Kittle, Jajuan Jennings, and give Brian Robinson more carries, instead of checking it down to McCaffrey at the rate Mac Jones was.

McCaffrey’s rushing efficiency (3.7 yards per carry) hasn’t been great, with limited holes to be found at the line of scrimmage. Combine that with the replenished options in the passing game, and we should see a down-turn in receiving volume. That will keep McCaffrey under a big yardage total, as Purdy spreads it around against the Panthers.

Anytime touchdown

Tetairoa McMillan (+145)

Though he’s played an extra game, coming into Week 12 McMillan has surpassed early Offensive Rookie of the Year betting-market darling Emeka Egbuka in receptions (nine more) and yards (31 more), with a statistical pace that makes him an interesting bet for the award at +450, compared to Egbuka at -135.

McMillan’s four touchdowns have come in pairs, but after catching just 56.6% of targets in his first seven games of his career, the Panthers’ burgeoning star has increased that rate by 10% from Young in the last four.

At 6-foot-5, McMillan’s got at least a half of a foot on the 49ers’ best cornerback, Deommodore Lenoir (5-10), and continues to be a prime target near the end zone.

Jalen Coker (+390)

After showing glimpses during his rookie season, Coker didn’t make his 2025 debut until Week 7, and after easing in for his first two games, Coker has moved past Xavier Legette for the second-most snaps (19 more) at wide receiver in the last three. Coker’s had four targets in each of the last two games, hauling in all four last week, plus a late two-point conversion.

Brycen Tremayne (18-1)/Mitchell Evans (14-1)

Consider this a public service announcement that, when it comes to a tertiary touchdown target in Carolina, just look for the Panther with the longest odds out of Brycen Tremayne, Ja’Tavion Sanders, Tommy Tremble and Mitchell Evans.

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Evans isn’t listed at BetMGM, but he’s widely available at +1400 — one of the four who play between one-third and one-half of the snaps. Sanders is the most reliable pass-catcher, and has the shorter odds, but he hasn’t scored yet, while Evans has two touchdowns this season.

This week, you can pair Tremayne and Evans together and split a half-unit on what amounts to 7-to-1 that one of them scores.

George Kittle (+120)

Even including a Sunday-night game with the Falcons, where Kittle returned from injury to be primarily a blocker in McCaffrey’s biggest game on the ground this season, Kittle’s scored in four of six games played this season. It’s reminiscent of a stretch where he scored in seven of eight games last season. Even just using those seven games with a touchdown out of 15 played, Kittle’s 46.6% rate makes +114 a fair price, before adjusting for a weaker defensive opponent, playing with Purdy and in a game where scoring is expected.

Ricky Pearsall (+195)

When healthy, it’s easy to make the case that Pearsall, the former first-round pick, is the 49ers’ No. 1 receiver. While McCaffrey and Kittle tend to score all the Niners’ touchdowns, Pearsall can strike from deep. Given he’s still looking for his first score of the season, there might be added incentive for a play to go his way near the end zone, if the Niners are having their way in this game – as the market seems to expect.

You can find more valuable betting analysis from Yahoo Sports betting contributor, Matt Russell, at THE WINDOW.