Clemson vs. Louisville Prediction and Game Preview

1. Louisville’s Ground Game
Louisville’s ‘25 offense isn’t the best Brohm has assembled at his alma mater, but this unit still enters Friday night’s matchup averaging 32.9 points a contest. And with the offense navigating some up-and-down play from quarterback Miller Moss, the Cardinals have been able to rely on the ground attack to lead this team into contention for the ACC title.

Leading rusher Isaac Brown (783) is expected to be sidelined on Friday night for the second game in a row due to injury. However, Brohm should be able to give Clemson’s defense a heavy dose of Louisville’s backfield that includes Keyjuan Brown (457 yards) and Duke Watson (83). In last season’s win in Death Valley, the Cardinals pounded the Tigers for 210 yards and three scores.

A repeat of 200-plus rushing yards won’t be easy for Louisville, however. Clemson ranks No. 37 nationally in defensive success rate against the run and limits conference opponents to just 3.7 yards a carry. The Tigers are better equipped to handle the Cardinals’ ground game than they were last season.

Can Brohm once again churn out a successful attack against Clemson’s front? Or will the Tigers stuff the run and put this game into the hands of Moss?

2. Clemson QB Cade Klubnik Against Louisville’s Defense
It’s strength versus strength when Clemson’s offense takes the field against Louisville’s defense. The Cardinals are giving up only 21.7 points a contest and rank second in the ACC in pass efficiency defense. Clemson’s passing attack hasn’t quite fired on all cylinders all year, but Swinney’s group ranks third in the ACC in passing yardage (288.4 a game), with quarterback Cade Klubnik passing for 2,136 yards and 14 touchdowns to just five picks.

After a sluggish start to ‘25, Klubnik has settled in over the last couple of contests. The senior threw for 385 yards and two touchdowns in a 46-45 loss to Duke and was steady (20 of 27 for 221 yards and a score) in last week’s win over Florida State.

Five Clemson players have over 20 catches this year, including Bryant Wesco (31 for 537 yards) and T.J. Moore (31 for 536). That duo, along with Klubnik, are a massive challenge for Louisville’s secondary, especially after California gashed this group for 350 yards last week. 

3. Louisville’s QB Miller Moss
Brohm is one of the top quarterback gurus in college football, but Moss - a transfer from USC - has struggled at times this season. The senior is completing 63.8 percent of his throws and has passed for 2,132 yards. However, Moss has tossed seven picks, has connected on just two throws of 40-plus yards, and ranks 11th in the ACC in quarterback rating.

If Moss has time to throw, Clemson’s secondary has been vulnerable to the pass and will give up a big play or two at times. Receivers Chris Bell and Caullin Lacy are the main targets for Moss, with both possessing the ability to make plays downfield or in space.

If Moss gets off to a slow start on Friday night, could Brohm turn to freshman Deuce Adams or Brady Allen? With a tight game expected, Moss needs to limit the mistakes and thrive in the short-to-midrange passing game (85 completions of 10-plus yards). 

Final Score Prediction: Louisville 27, Clemson 24

Not having Isaac Brown is significant for Louisville, and Moss’ up-and-down play is certainly a reason to be concerned for the Cardinals on Friday night. However, Brohm should be able to get this team back on track after last week’s loss and focused on finishing the year with three consecutive victories. A win by Clemson wouldn’t be a surprise. But a slight edge goes to Louisville at home. 

ATS: Louisville - 2.5
Over/Under: Under 51.5