Clemson vs. Louisville prediction, odds: Week 12 college football picks by proven model

The 15th-ranked Louisville Cardinals look to keep their conference championship hopes alive when they battle the Clemson Tigers in a key ACC 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.

Kickoff from L&N Federal Credit Union Stadium in Louisville, Ky., is at 7:30 p.m. ET. The Cardinals are 2.5-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 Louisville vs. Clemson picks, check out the college football predictions from the SportsLine Projection Model. 

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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. Anybody following its college football betting picks at sportsbooks and on betting sites could have seen strong returns.

Now, the model has set its sights on Clemson vs. Louisville. You can visit SportsLine now to see the picks. Here are the FBS college football odds and trends for Louisville vs. Clemson:

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How to make Clemson vs. Louisville picks

SportsLine's model is going Over on the total (50.5). The Tigers have gone over in four of the past six games, while the Cardinals have gone over in six of their last 10. Clemson quarterback Cade Klubnik is projected to pass and run for a pair of touchdowns, while Louisville signal caller Miller Moss is projected to pass for more than 220 yards and two touchdowns, while rushing for another. The teams combine for 54 points as the Over clears in well over 50% of simulations. 

The model also says one side of the spread hits over 50% of the time. You can only get the pick at SportsLine. 

So who wins Clemson vs. Louisville, and which side of the spread hits more than 50% of the time? Visit SportsLine now to see which side of the Clemson vs. Louisville spread to jump on, all from the advanced model that finished up over $2,000 on its FBS college football picks since its inception, and find out.