Louisville football's 2025 ACC game-by-game predictions: Can Cardinals win the ACC?

With the Cardinals' ACC schedule kicking off this week against Pitt in Week 5, here are our final game-by-game predictions for Louisville football in the 2025 season.
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Week 10: vs Clemson (Nov. 14th)

Well, this massive Friday night showdown quickly turned into a must-win game for the Cardinals. Clemson is the biggest disappointment of the 2025 season so far, as the Tigers are 1-3 after falling to Syracuse yesterday, 34-21.

The Tigers have seen their ACC Title odds disappear, and Louisville is now one of the top four teams. The Cardinals will have to play just like they did last year and dominate the trenches and be the more physical team. Entering the season, this was thought to be a loss for the Cardinals, but now, with Clemson falling to Georgia Tech and Syracuse, Louisville should take down the Tigers for the second straight year, and the second time in program history.

Prediction: Louisville 34 Clemson 24

Related: This three-game gauntlet will define Louisville football's fate in 2025

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