Louisville vs. Clemson Prediction, Odds, Picks - November 14, 2025

Two of the nation's top run defenses meet when the No. 19 Louisville Cardinals (7-2) bring college football's 22nd-ranked rushing defense into a matchup with the Clemson Tigers (4-5), who have the No. 20 rushing defense, on Friday, November 14, 2025. The Cardinals are only 2.5-point favorites. The over/under is set at 50.5 for the contest.

Last time around, the Cardinals fell to the California Golden Bears, with 29-26 being the final score. The Tigers beat the Florida State Seminoles, 24-10, in their most recent contest.

Keep up with college football all season on FOX Sports.

Louisville vs. Clemson Game Information & Odds

• When: Friday, November 14, 2025 at 7:30 p.m. ET
• Location: L&N Federal Credit Union Stadium in Louisville, Kentucky
• TV: ESPN
• Live Box Score on FOX Sports

This page may contain affiliate links to legal sports betting partners. If you sign up or place a wager, FOX Sports may be compensated. Read more about Sports Betting on FOX Sports.

Louisville vs. Clemson Prediction

• Pick ATS: Louisville (-2.5)
  
• Pick OU: Over (50.5)
  
• Prediction: Louisville 31, Clemson 20

Predictions are made by the Data Skrive betting model.

Learn more about the Louisville Cardinals vs. the Clemson Tigers game on FOX Sports!

Louisville vs. Clemson Betting Insights

• Per the spread and over/under, the implied score for the matchup is Cardinals 26, Tigers 24.
• The Cardinals have a 56.5% chance to claim victory in this meeting per the moneyline's implied probability. The Tigers hold a 47.6% implied probability.
• Louisville is 3-6-0 ATS this season.
• Clemson has put together a 3-6-0 ATS record so far this season.

Louisville vs. Clemson: Head-to-Head

• Clemson holds a 2-1 record against Louisville in their last three matchups.
• In those games against Louisville, the Tigers have covered two times while outpacing the total on one occasion.
• In their last three head-to-head matchups, Clemson has scored 82 points versus Louisville, while surrendering only 73 points.

Louisville vs. Clemson: 2025 Stats Comparison

Louisville 2025 Key Players

Clemson 2025 Key Players

FOX Sports created this story using technology provided by Data Skrive and data from Sportradar.

Want great stories delivered right to your inbox?

Create or log in to your FOX Sports account, follow leagues, teams and players to receive a personalized newsletter daily.