The Clemson Tigers and Louisville Cardinals will do battle in the ACC on Friday night. Clemson enters at 4-5 overall (3-4 in the ACC) and is fighting to preserve its 26-year streak of non-losing conference campaigns. Louisville is 7-2 (4-2 ACC) and looks to bounce back after a costly home loss. Before this game kicks off from Kentucky, continue reading to get my Clemson vs Louisville prediction.
Our Clemson vs Louisville Pick
Pick: Louisville -3
Confidence: ★★★★☆
Game Snapshot
- Matchup: Clemson Tigers vs Louisville Cardinals
- Date & Time: Friday, November 14, 2025, 7:30 p.m. ET
- Venue: L&N Federal Credit Union Stadium, Louisville, Kentucky
- Broadcast: ESPN
Key Storylines
This is about responding for Louisville. The Cardinals were upset at home by the California Golden Bears in overtime in their last game. That game dropped them to 20th in the country and dropped them behind several teams in the ACC standings. They must guard against a let-down heading into this high-profile league game, as they could fall out of the rankings entirely with a loss here.
Clemson has had its struggles this season. They enter this game at 4-5 and they are scrambling for bowl eligibility and trying to avoid their first losing ACC campaign in decades. They ended a two-game losing streak in their last outing by beating a Florida State team that is also struggling. But it has been a disappointing season to say the least for the Tigers.
Quarterback Play
Clemson’s senior quarterback Cade Klubnik has thrown for 2,136 yards this season with 14 touchdowns and 5 interceptions. Yet despite those numbers, Clemson’s offense has lacked consistency and their rushing attack has been underwhelming.
Louisville QB Miller Moss has logged 2,132 passing yards, 11 touchdowns, and 7 interceptions. The highs have been high and the lows have been low for Moss this season. He will try to bounce back from an underwhelming showing against Cal. Louisville must rely on their run game to steady the offense and avoid putting Moss under pressure.
Betting Trends
- Louisville is 3-6 against the spread this season despite a strong 7-2 straight-up record.
- Clemson is 3-6 against the spread this year as well.
- The Tigers have gone 3-5-1 on over/unders so far this season.
- Louisville has gone over the total in five of its first nine games entering this game.
Clemson vs Louisville Model Projection
Score Projection: Louisville 28 – Clemson 20
Win Probability: Louisville 60%, Clemson 40%
Final Thoughts
I’m expecting Louisville to bounce back from their underwhelming performance last time out by beating the Clemson Tigers at home here. Clemson hasn’t beaten anyone respectable in the ACC yet and I don’t expect them to here either. I will lay the field goal with the Cards, while Clemson will be forced to win its final two games of the season if they want to see bowl season.
