Clemson vs. Louisville Prediction & Betting Picks (November, 14th, 2025)
The Clemson Tigers can see their season slipping away from them at 4-5, and a brutal road test against the Louisville Cardinals doesn’t figure to be the cure to what ails them.
Dabo Swinney’s crew enter as a mild +110 road underdog, even though they haven’t done much on the year to deserve that kind of respect. Louisville has been the better team this season and will look to add to a 7-2 record, while staying within striking distance of first place in the crowded ACC.
This game is priced suspiciously close, which could either be a sign that bettors shouldn’t overlook Swinney’s Tigers, or that it’s time to pounce on the value associated with a good Cardinals team.
Not sure which side to back? I’ll break down the latest odds and matchups, working my way to my top picks and a Clemson vs. Louisville prediction.
Game Basics & Context
- Matchup: Clemson Tigers (4-5) vs. Louisville Cardinals (7-2)
- Date & Time: Friday, November 14th, with kickoff at 6:30 pm CT (7:30 pm ET)
- Venue: L&N Stadium in Louisville, KY
- How to Watch: The game will be broadcast on ESPN.
Team Record
- Clemson is 4-5, 3-4 in the ACC.
- Louisville is 7-2, 4-2 in the ACC.
Betting Odds
Check out the most current Clemson vs. Louisville odds, per DraftKings:
| Team | Spread | Moneyline | Total |
|---|---|---|---|
Clemson | +2.5 (-112) | +110 | O 50.5 (-115) |
Louisville | -2.5 (-108) | -130 | U 50.5 (-105) |
Rivalry & Venue Context
Clemson and Louisville have not faced each other very much, with just nine total meetings in their history. The Tigers have dominated the series, going 8-1 in the process.
The most recent meeting is probably the most accurate depiction of where this matchup is at, as Louisville finally stole a win in the series with a convincing 33-21 victory in 2024.
Clemson had gotten off to an 8-0 start in the series before that, although Louisville gave them a tough fight back in 2021 in a 30-24 thriller.
The game will be played at L&N Stadium, where the Cardinals are actually just 4-2 on the year. Both losses were fairly understandable (and close), as they dropped tight thrillers versus California and Virginia.
Why This Game Matters
Clemson’s season is already over. They’d need to win out for a shot at a bowl game. Perhaps they can sniff one just because of who they are, but they’re playing for pride for the most part at this point.
Playing spoiler can be fun, but Louisville is at home with the rest of their season still in front of them. Nobody is throwing shade at the Cardinals for close losses to Virginia or Cal, but dropping this one at home would be pretty devastating.
Louisville still has a shot at the ACC title, while there’s a window for a run at the College Football Playoff. They certainly have their sights on a top-shelf bowl game at the very least, but avoiding a loss to an inferior opponent on Friday is absolutely critical.
Team Profiles
Clemson Tigers
Clemson has an all-time great coach and a team loaded with talent and potential, but they really haven’t seen the results they typically do in 2025.
The Tigers haven’t exactly been awful, as they have been in most of their games. They’re coming off a nice 24-10 win over Florida State in their last game, while of their five losses, three have come by one score, and none have been by more than 13.
One of their losses was arguably one of the best games of the year, where they fell to Duke, 46-45. Clemson has a plenty capable offense (27.9 points per game), while they have a very good passing game that puts up over 288 passing yards per contest.
Unfortunately, the Tigers can’t run the ball very well, and they give up a lot of production through the air on the other end. Their run defense is elite, and they are respectable in terms of points allowed per game.
Louisville Cardinals
There’s no denying that the Cardinals are the better team compared to Clemson. Record aside, Louisville has been super consistent on offense, scoring at least 24 points in every single game this season.
That has translated to the nation’s 41st-best scoring offense, as they are putting up over 30 points on average. More than raw points, Louisville is extremely balanced and tough to predict or stop.
Louisville has been led by two explosive running backs in Isaac Brown (782 rushing yards) and Keyjuan Brown, who both average well over six yards per carry. That hasn’t led to one of the nation’s best ground games by the numbers, but that bleeds into their overall balance.
Things do change with Brown being out with an injury, but Brown is capable of carrying the torch for Louisville’s ground game.
Assuming he can, this is just not a very easy offense to stay in front of. On top of that, the Cardinals are decent defensively. They do give up over 22 points per game, but they tend to smother opponents, ranking 21st against the run and 35th against the pass.
Key Matchup Angles
Consider the following key matchups:
- Clemson’s ground game vs. Louisville’s run defense: The Tigers aren’t particularly great on the ground, but it will be interesting if they can muster any success against a Louisville unit that has been holding the opposition to just 113 total rushing yards per game.
- Louisville’s ground game vs. Clemson’s run defense: The Cardinals aren’t an elite rushing attack, but they’re not far off. They still put up 145.9 yards per game on the ground and have a nice stable of RBs to tire out Clemson. That said, the Tigers (17th) have been even nastier against the run. Whether they miss Brown or not could contribute to the importance of this matchup, though.
- Louisville’s RZ defense vs. Clemson’s RZ offense: The Cardinals do not give up much production, but when teams get close, they’re not elite at keeping them out of the end-zone. Whether that holds up against a decent Tigers RZ offense will be key to this game.
Betting Insights & Trends
Unsurprisingly, the Tigers have not been very reliable (3-6) against the spread. The Tigers are 2-1 against the spread as the road team, though, while they are 3-4 ATS in ACC clashes.
Louisville has a good record, but they do allow teams to stay close at times. They are just 3-6 ATS in 2025, while they are a putrid 2-6 against the spread when favored.
Best Bets & Confidence Levels
Check out my favorite Clemson vs. Louisville picks:
| Bet | Recommendation | Confidence Level |
|---|---|---|
Louisville -130 | The ATS data is troubling, but there isn’t a large spread to exploit. Ultimately, we’re talking about a much better team at home in a primetime setting. I have no interest in bypassing the Cardinals at this -130 price. | 7/10 |
Over 50.5 (-115) | Both of these teams can be respectable on defense, but they’re not elite. The Cardinals specifically grade out very well against the run and pass, but they buckle too much in the RZ. When adding the offensive talent and upside into the equation, this total feels a little too low. | 7/10 |
Prop Play – Keyjuan Brown Anytime TD (-135) | Keyjuan is looking at a huge workload with his running mate sidelined. Clemson’s run defense can be tough, but if Louisville is going to score (and there’s no reason they won’t), their top RB is a good bet to do the damage. | 7/10 |
- Primary Pick: Louisville ML (-130)
- Secondary Pick: Over 51.5 (-115)
Louisville has too much on the line to cough up a loss to an inferior opponent at home. After already getting tripped up last week, look for them to be focused and bounce back with a big win against Clemson.
The game total is also pretty palatable where it stands. Both teams have solid offensive upside, and neither defense is so good that they are reliable threats to shut the other down.
With Isaac Brown out, his backup steps into a huge role. On top of the natural volume he’ll see, he is a good bet to see red-zone carries and fall into the endzone at least once.
Clemson vs. Louisville odds are shifting fast — track every line move and secure the best spreads before kickoff. Compare real-time odds now at the top football betting sites.
Risk Factors & What Could Go Wrong
There are no guarantees when betting on sports. Here’s why these Clemson Tigers vs. Louisville Cardinals bets could fail:
- Tough Out: Clemson has a bad record, but they’ve been a tough out for much of the year. They barely lost to Duke and just dominated Florida State. It isn’t crazy to think they could come into Louisville and stage the upset.
- Coaching Matters: If we wanted to look at this game simply from a coaching perspective, we’d be scared to go away from Dabo. He’s a legendary coach with titles in his back pocket. Motivating and leading Clemson back to .500 is definitely in play.
- Defensive Bite: I like the Over on a palatable game total, but what if the defenses show up? Both teams are extremely stingy against the run, so it isn’t too wild to imagine a game where the offenses turn one-dimensional and struggle.
Putting Our Pick on the Board: Here’s How It Plays Out
Final Score Prediction: Louisville Cardinals 30, Clemson Tigers 27
Louisville has dropped two games on the year, and they both went down to the wire. To their credit, Clemson has been in most of their games thanks to solid coaching and a respectable defense.
I don’t see Clemson shutting Louisville down, and while both defenses are good, they aren’t stingy enough to fear the Under. This is a big game for both teams, but it means a lot more for the Cardinals.
With so much at stake, Clemson should show up to play spoiler, but the better team should have the last laugh in front of their home crowd.
