Clemson vs Louisville Prediction, Spread & Picks for Friday Night ACC Clash

• Clemson battles Louisville in Friday Night ACC action
• The Tigers are 6-1 ATS in their last 7 games against the Cardinals
• Check out my Clemson vs Louisville predictions, spread & picks below

Clemson meets Louisville in a Friday night ACC clash at Federal Credit Union Stadium. The Tigers enter off a 24-10 beatdown of Florida State, but have lost two of their last three contests. Meanwhile, the Cardinal are nursing their wounds after they suffered a 29-26 overtime loss against Cal as 15-point favorites.

Catch all the Clemson vs Louisville action on Friday November 14th on ESPN, with kickoff set for 7:30 pm ET.

Time to profit. Find my Clemson vs Louisville prediction, spread and picks, below.

Clemson vs Louisville Prediction

• Pick: Louisville ML (-142)

FANDUEL SPORTSBOOK

Offer

T&Cs

Bet $5 & Get $150 in Bonus Bets if Your Bet Wins

Must be 21+. T&C Apply. Gambling Problem? Call 1-800-GAMBLER.

LOCK IN PROMO

SIGNUP PROMO

BET $5
GET $150

BET NOW

Jeff Brohm has shown an ability to motivate his team after losses during his tenure in Kentucky, going 5-2 SU after a regular-season loss. One of those victories came over a stacked Miami team as a double-digit underdog, so the Cardinal will be far from afraid of Dabo Swinney’s underachieving Tigers.

Remember, Louisville won a 33-21 decision on the road in Death Valley last season as 11-point dogs. The Louisville secondary ranks 14th nationally in EPA allowed per pass, and the Cardinal defense is 21st in overall offensive success rate. Louisville also holds a higher net EPA per drive than Clemson and have a positive turnover differential on the season.

I like the Cardinal to come out on top, at home, against a Clemson Tigers squad that struggles to run the football. Look for Louisville to force Clemson to throw the football early and often, capitalizing on the Tigers’ mistakes.

Clemson Betting Analysis

Once one of the favorites to win the College Football Playoff, Clemson’s 2025 season has been a disaster. The pre-season ACC favorites have floundered to a 4-5 record, with embarrassing losses to SMU and Syracuse.

Quarterback Cade Klubnik was viewed as a Heisman Trophy contender and potential first-round NFL Draft pick in August, but he’s thrown for just 2136 yards and 14 touchdowns with five interceptions. Klubnik looked shaky in the pocket for most of the season, and along with his Tigers’ teammates, fell well short of expectations.

The Tigers are 4-5 on the year, sit 119th in rushing EPA per play, are an average defensive team despite their plethora of NFL talent, and can’t seem to get out of their own way. Sloppy penalties and untimely turnovers have killed the Tigers momentum, and a visit to play Louisville’s superb defense will do little to help those problems.

Keep in mind, Clemson is 4-10 ATS in its last 14 games, and 13-5 SU in its last 18 contests against ACC opponents.

Louisville Betting Analysis

Buoyed by a top-tier defense allowing just 4.7 yards per play, the Louisville Cardinal are chasing an ACC title. Brohm’s squad ranks 14th nationally in EPA allowed per drive, and are surrendering just 315 yards per game. On top of that, opponents are converting only 35% of third downs against the Cardinal, good for 32nd in the country.

The Cardinal stop-unit creates havoc, leading to 16 takeaways on the year. Louisville’s sticky cornerbacks play tight coverage, forcing opposing passers into tight window throws.

On the offensive side of the field, quarterback Miller Moss has been average. The USC transfer has tossed for 2,132 yards and 11 touchdowns, but averaged just 6.9 yards per pass while throwing seven interceptions and taking 18 sacks.

Thankfully, the Cardinal’s two-headed rushing attack led by Isaac Brown and Keyjuan Brown has taken the pressure off their signal-caller. Isaac leads the team with 782 yards on a wild 8.6 yards per carry, but he’ll miss a second-straight game with a lower leg injury. In his stead steps Keyjuan, who’s put up just 6.9 yards per carry with six rushing scores.

Louisville are 10-2 SU in their last 12 games, but 0-6 ATS in their last six contests at home.

Clemson vs Louisville Odds

Louisville are 2.5-point favorites in the Week 12 college football odds. The Clemson vs Louisville total is set at 51.5 with the under favored at -115, and the over sitting at -105.

Bettors are split on this one, as 73% of moneyline wagers are on the Cardinal, but 53% of spread tickets like the Tigers in the college football public betting splits.

Odds as of November 12th at FanDuel. Find the best college football betting apps for Clemson vs Louisville.