Clemson vs. No. 15 Louisville odds, line: 2025 college football picks for Week 12 predictions from proven model

The 15th-ranked Louisville Cardinals look to keep their conference championship hopes alive when they battle the Clemson Tigers in a key Atlantic Coast Conference matchup on Friday. Clemson is coming off a 24-10 win over Florida State, while Louisville looks to rebound from a 29-26 loss to California last Saturday. The Tigers (4-5, 3-4 ACC), who are 10th in the conference standings, are 2-1 on the road this season. The Cardinals (7-2, 4-2 ACC), who are sixth in the league, are 4-2 on their home field in 2025.

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Kickoff from L&N Federal Credit Union Stadium in Louisville, Ky., is at 7:30 p.m. ET. Clemson leads the all-time series 8-1, but Louisville won last year's meeting 33-21. The Cardinals are 1.5-point favorites in the latest Clemson vs. Louisville odds, while the over/under for total points scored is 50.5 via SportsLine consensus. 

Before making any Clemson vs. Louisville picks, be sure to check out the college football predictions and betting advice from the SportsLine Projection Model.

The model simulates every FBS game 10,000 times. Since its inception, it has generated a betting profit of over $2,000 for $100 players on its top-rated college spread football picks. Anyone following could have seen impressive returns.

The model has simulated Clemson vs. Louisville 10,000 times and the results are in. We can tell you that the model is leaning Over, and it also says one side of the spread hits more than 50% of the time!

So who wins Clemson vs. Louisville, and which side of the spread hits more than 50% of the time? Join SportsLine right now to see which side of the spread you need to jump on, all from the computer model that has crushed its college football picks!

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