Louisville 2025 game-by-game predictions: Can Cardinals beat Clemson again?

With fall camp starting up, 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)

In what will be their third Friday game of the year, Louisville will host Clemson at L&N Stadium come mid-November. Clemson comes to Louisville as a perennial ACC power, as even in what was considered a “down year” in 2024, they went 10–3, finishing second in the ACC, and won the ACC Championship.

Star quarterback Cade Klubnik returns for his senior season and will hope to improve on what was a pretty mediocre year for him (2,739 yards 19 TDs and 10 INTs). The top pass catcher and running back from 2024 each have moved on, but Klubnik will still have plenty of talent around him.

Even with a playoff- experienced QB, the real strength of this Clemson Tiger’s team is their defense. Clemson’s front seven is nasty again, headlined by Peter Woods and T.J. Parker. The secondary is one of the best in the country, with Avieon Terrell and Kylon Griffin anchoring it.

The Louisville offense will have its hands full, and have to play extremely mistake free in order to hand Clemson its second upset loss in two years in this new ACC rivalry.

Prediction: L (8-2) Clemson 27 - Louisville  17

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