Clemson vs. #20 Louisville Picks and Predictions: Friday Night in the ACC

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It's been a disappointing year for Dabo and the Tigers - Clemson Louisville Picks

We have made it to another wonderful weekend and it truly begins with some Friday Night Lights in the ACC. The No. 20 ranked Louisville Cardinals host the Clemson Tigers who just want their disappointing season to end. Tonight the two teams go head to head in what was supposed to be a much more meaningful game going into the season, however there are still some major implications at play for both schools. Let’s break it down and get into our favorite picks.

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Clemson Tigers vs. #20 Louisville Cardinals NCAA Football Insights

Cade Klubnik and Clemson have not lived up to expectations this year - Clemson Louisville Picks

Cade Klubnik and Clemson have not lived up to expectations this year

Although Clemson’s season has been a dumpster fire considering they had a Heisman favorite at quarterback and were picked to win the ACC, they can still go bowling. The Tigers sit at 4-5 on the season, needing two wins in their final three games to be bowl eligible. Their remaining schedule? At Louisville this week, against Furman, and then at South Carolina. Yes, the Paladins are probably an automatic win, but those other two are not, leading me to think we get the best effort possible out of this Tigers team tonight.

As for the hosts, they still have plenty to play for. They don’t control their own destiny into the ACC Championship anymore, but could still make a case if things get freaky towards the top of the standings. That head to head win over Miami is certainly propping them up, but the Cardinals can’t help but think they would be undefeated had both overtime contests gone their way. Nevertheless, three wins to end the year is all they can hope for (along with rooting for chaos).

Matchup Information – Clemson vs. Louisville – November 14

  • Venue & Location: L&N Federal Credit Union Stadium (Louisville, KY)
  • Date: Friday, November 14, 2025
  • Kick Off: 7:30 p.m. Eastern
  • Broadcast: ESPN

Clemson vs. Louisville Betting Odds

Odds are courtesy of BetOnline, one of our favorite online sportsbooks, as of November 14, 2025 at 9:53 a.m. eastern. Sign up today with Promo Code BNBOL55 for a 55% deposit bonus. BetOnline offers a wide variety of unique markets across nearly every sport imaginable.

Spread

  • Clemson +2.5 (-113)
  • Louisville -2.5 (-107)

Moneyline

  • Clemson +106
  • Louisville -126

Total

  • Over 51 (-118)
  • Under 51 (-102)

Both teams are coming off a short week, but the hosts are responding after an overtime loss at home to a 6-4 California team. They have much more to play for than Clemson (in my eyes), and even with the line ticking down, I expect them come prepared to handle business.

Clemson vs. #20 Louisville NCAA Football Picks and Predictions

Miller Moss has over 2,100 passing yards and 18 total touchdowns - Clemson Louisville Picks

Miller Moss has over 2,100 passing yards and 18 total touchdowns

Clemson vs. Louisville Prediction: Louisville Wins and Covers, Under 51

Best Bet: Louisville ML (-126) BetOnline

Clemson has zero wins against teams that are better than them. Their four wins are over Troy, at North Carolina and Boston College, and against Florida State. The Tar Heels are 2-3 in the ACC, FSU is 1-5, and Boston College still doesn’t have a conference win and sit at 1-9 on the year. Earlier this season, the Tigers lost to Georgia Tech (8-1), Syracuse (3-7), SMU (7-3) and Duke (4-1 in ACC). Louisville is 7-2 overall, has lost just twice this season by a combined six points, and they have the benefit of being at home. The Tigers cannot play with the big boys this year.

Clemson’s offense is all pass; they have no run game, ranking No. 91 in yards per carry but are top 25 in pass play percentage, throwing over 55% of the time. Louisville has an extremely good secondary that will be able to shut them down. The Cardinals rank top 25 in opponent completion percentage and top 11 in opponent interceptions thrown and yards per pass allowed.

I do not see Clemson moving the ball at all. The argument for a Louisville look ahead to SMU next week could be there, but they’ll have an extra day given they play on Friday, so I believe they’ll be fine.

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