The Clemson Tigers head to Louisville on Saturday as a reeling Cardinals team looks to rebound after losing to California. The Tigers, meanwhile, will look to continue riding the good vibes generated by a win against Florida State.
Take a look at my early Clemson vs. Louisville predictions and college football picks for Friday, November 14.
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Clemson vs Louisville predictions
Here are our early thoughts on the spread and total for this week’s game. We will have a full game preview (with a best bet and SGP) later in the week.
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Early Clemson vs Louisville spread pick: Louisville -3.5
This is a Jeff Brohm spot in the same way last week was a Jeff Brohm spot to inexplicably lose.
There have been 18 losses to conference opponents as a favorite of -15 or bigger over the last two seasons in college football. With the loss against California over the weekend, the Louisville Tigers now have two of them, but like I said, just as these blunders have become synonymous with the Jeff Brohm tenure at Louisville, so has his ability to pick his teams up after them, especially against the big brands on the schedule.
Brohm has gone 5-2 during the regular season after a loss at Louisville, and one of those wins came this season against Miami as a double-digit underdog.
He’s also 1-0 head-to-head against Dabo Swinney in his coaching career, winning as an 11-point underdog last season. Enough of the situational stuff, though: this game favors the Cardinals on the field, too.
Even with its sure-fire NFL talent Isaac Brown missing a second straight game, Louisville should be able to run the ball pretty well against a Clemson Tigers front that has allowed explosive runs at a nearly 7% rate this season (32nd percentile).
On the other side of the ball, this Cardinals defense should be able to control things. Clemson simply can’t run the ball, and although it had a very bad week against California, this Louisville secondary has looked strong this season, ranking 14th nationally in EPA allowed per dropback.
Early Clemson vs Louisville total pick: Under 51.5
I like the Under with a projection of 49.5. Both offenses have real limitations, and both defenses are built to expose them, which should keep drives short and the clock moving.
For Louisville, Miller Moss has simply been poor. Against Cal, he went 20 of 38 with a key interception and missed several makeable throws. Pressure has been the common thread in his worst moments, and Clemson has produced an above-average havoc rate this season.
There's chatter about a potential quarterback change, but even if that happens, the identity likely stays the same. Louisville’s best path is a methodical, run-first approach that limits risk, shortens the game, and suppresses total possessions.
On the other hand, I will take this opportunity to buy low on the Louisville defense, especially with a ballhawk secondary that could be a bit healthier this week. We’ve waited for quarterback Cade Klubnik to become the guy, and this season answered that question with finality: he isn’t.
Louisville can contest throws, generate a takeaway or two, and force field goals instead of touchdowns. I’ll take this game to be a bit of a grinder, mostly because the play behind center has been subpar — to put it kindly — for both teams.
Clemson vs Louisville odds
- Clemson vs. Louisville spread: Louisville -3.5
- Clemson vs. Louisville moneyline: Clemson +140, Louisville -165
- Clemson vs. Louisville Over/Under: 51.5
How to watch Clemson vs Louisville
- Clemson vs. Louisville matchup
- Date: Friday, November 14, 2025, 7:30 p.m. ET
- City: Louisville, KY
- Venue: L&N Federal Credit Union Stadium
- TV: ESPN
Odds are correct at the time of publishing and are subject to change.
Not intended for use in MA.
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