Monday Night Football Picks: Carolina Panthers vs San Francisco 49ers

by Mike Allen - 11/20/2025

Are you ready for some football?! I've been a fan of Chris Stapleton since "Tennessee Whiskey", but you can't replace Bosephus that easily. I remember my dad reaching for the remote so fast to adjust the volume, so as not to wake my mother, when Hank Williams Jr. exclaimed those six sexy words we began with today.

On a positive note, I do hate on Carrie Underwood a bit, but imagine if that were Taylor Swift. The Manningcast would blow up even bigger! George W. Bush was on last week and told them it’s nice to see you guys NOT on a commercial.

Enough about the trials and tribulations of Monday Night Football. It’s time to pick a San Francisco 49ers game, which requires a ton of focus as well as completely illogical thinking. I’m kidding, but I’m really not.

I’ve improved steadily over the past few years, picking primetime games early in the week. The 49ers are a popular team. Naturally, I get to break them down from a betting perspective several times per season.

They have been such a struggle for me, and a betting friend in Ohio mentioned they're pretty much owned by the Youngstown Mob, and it made perfect sense, but only to my ego. Most of my peers agree with me, though, that the Niners are not an easy team to nail down. They haven't been for a while.

In their defense, I just wrote on the Buccaneers and said they may be the most injury-riddled NFL team of 2025, but the Niners aren’t far behind. For them, it’s been on both sides of the ball, including being without starting quarterback Brock Purdy for several weeks. As a replacement, Mac Jones played alright. Some were even saying that he wasn’t that big of a step down from Purdy.

While Jones is one of the better backups in the league, Purdy is still a tick better. It’s expectations. People had nearly none for Jones because he’s the backup. As long as he didn’t implode, he did a decent job.

Purdy’s expectations are not the same, especially after last week’s triumphant return to action in the 41-22 win over the Arizona Cardinals. He was surgical, throwing for 200 yards and 3 TDs on just 19/26 passing.

I like to read some of the local beat writers’ articles before I break a game down. That’s where you’re gonna get that next level of understanding. A few made the same point that Purdy’s intangibles make up for his lack of superior physical attributes.

Niners fans were immediately reminded on Sunday why he’s their guy.

As for the Carolina Panthers, well, they aren’t the most consistent squad either, especially lately. After beating the Packers at Lambeau Field, they immediately lost to the Saints at home by double digits.

Other than that, though, I guess they’ve been pretty consistent, losing big to teams like the Bills and Patriots but have taken care of business twice against Atlanta, as well as wins over the Jets, Cowboys, and Dolphins.

Are you seeing what I’m seeing? The Panthers have had a pretty easy road to get here. After the Niners, they still have to play the Rams, Seahawks, and then the Buccaneers twice.

One thing the Panthers have going for them this week is desperation. They’re 6-5 and can’t afford to lose many more games if they want a chance at the postseason.

Doc’s Sports offers NFL expert picks for every game on our NFL predictions page.

Carolina Panthers (+7) at San Francisco 49ers (-7)

We opened at 6, and the Circa actually still has this game at (-6.5) for the favored Niners. They’re one of the sharper sportsbooks, but they’ll have to move the line to 7 by kickoff because the Niners are the public side.

Point Total: 49.5

The point total opened at 46 and was quickly hammered up to 49.5. This game and the Sunday night game have identical point totals and moneyline odds.

The Panthers seem like an under team, while the Niners, who are still banged up on defense, appear to be an over team with Purdy's return.

Moneyline Odds

Panthers: +270

49ers: -350

Carolina Panthers at San Francisco 49ers Betting Analysis

I mention Sunday Night Football because if the Bucs lose, and their moneyline currently has an implied probability of 27%, the improbable Panthers could move into first place in the NFC South with a victory.

That would be cool, but outside of the Green Bay win, the Panthers have zero solid performances against quality teams. Looking at the box score for that game, Green Bay had 5.9 yards/play to the Panthers' 4.9 and didn't even punt the ball once. Green Bay had 2 turnovers to Carolina's 1, but it was on trips to the red zone where the Panthers' defense shone, holding them to just 1 touchdown after 5 red zone visits.

With the Niner offense returning to health, they could blow out the Panthers here, much like they did the Cardinals on Sunday.

The San Francisco defense, though, is decimated. They’re without their leader, Fred Warner, and the best player on defense, Nick Bosa. Add in linebacker Tatum Bethune’s questionable injury status, and you can see why the money poured in on the over.

Carolina can certainly be blown out, though. The Bills and Pats did it with superior passing attacks. In low-scoring games, the Panthers will always have a chance, but they're weaker against the pass than they are against the run on defense, and they typically need to establish the run to pass on offense.

I see them falling behind by two scores in the 2nd half, and this one playing out much like the Pats and Bills games vs the Panthers.

Carolina Panthers at San Francisco 49ers Betting Pick

Pick: San Francisco 49ers (-7)

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Pick:	Cincinnati +170
Start:	November 23, 2025 @ 5:00 PM
Expert:	Doc's Sports

Analysis:

Free Play from Doc’s Sports. MLS Take Cincinnati +170 over Inter Miami (5 p.m. EST, Sunday November 23) (Graded after regulation time - 90min - plus injury time – a DRAW is a loser here) This line is the Messi Effect as there is great value on the Orange and Blue here at home at TQL Stadium for this single- elimination playoff match. Cincinnati got the advantage of playing at home by having a better record, and the fact that they are above Miami in the standings yet an underdog here at home tells you all you need to know about where the bookies expect the money to come in on this one. Messi is the biggest draw in MLS and he brings in all the cash. But this will be no easy match for Inter Miami. Miami has just two road wins in eight matches since the summer. They are just not as good of a team on the road as they are at home. Cincinnati is a very good team. Last time Miami visited, in July, they held Messi in check but came up big offensively in a 3-0 win. They have a +8 goal differential in their last two home matches against Miami. Just really great value here at this price and we expect Cincinnati to go through to the conference finals. Read More Read Less

Monday Night Football Picks: Carolina Panthers vs San Francisco 49ers

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