Nov 8, 2025; Louisville, Kentucky, USA; Louisville Cardinals defensive lineman Wesley Bailey (23) reacts after sacking California Golden Bears quarterback Jaron-Keawe Sagapolutele (3) during the second half at L&N Federal Credit Union Stadium. California defeated Louisville 29-26. Mandatory Credit: Jamie Rhodes-Imagn Images

On Friday night, we'll be treated to an ACC battle with potential College Football Playoff stakes — at least for one team.

Coming off an overtime loss to Cal, Louisville (7-2, 4-2 ACC) looks to keep its ACC title and CFP hopes alive as it plays host to Clemson (4-5, 3-4 ACC), which arrested its slide in conference play last week with a 14-point win over Florida State.

The Tigers are fighting for bowl eligibility, but they're running into a Cardinals squad facing a must-win game.

Stream Louisville vs. Clemson

If you are looking for some betting advice for the matchup, we've got you covered. Here are the latest odds for the game, courtesy of BetMGM.

Louisville vs. Clemson game odds:

All college football odds via BetMGM

  • Spread: Louisville -2.5 (-115), Clemson +2.5 (-105)
  • Money Line: Louisville -140, Clemson +115
  • Over-Under: Over 51.5 (-105), Under 51.5 (-115)

Louisville vs. Clemson prediction, pick:

Louisville's offensive success has been hampered a bit with the injury to leading rusher Isaac Brown, though backup Keyjuan Brown is averaging nearly seven yards per carry and has over 450 yards on the season. The Cardinals have had to rely on the run quite a bit this year, as the passing game with Miller Moss has left a decent amount to be desired.

The real story here will be Louisville's defense. It's a top-25 unit in both success rate and EPA/play, and it's a well-rounded unit that creates a lot of havoc. It will need to play well against a Clemson offense that has been relatively successful thanks to its talent at the skill positions despite poor offensive line play.

The Cardinals will have to find a way to score some points here, unless they deliver a defensive masterpiece, but they should be able to eke this one out at home.

Prediction: Louisville 27, Clemson 21

Best Bet: Louisville -2.5, Under 51.5

Louisville vs. Clemson channel, start time, streaming:

Time: 7:30 p.m. ET

TV Channel: ESPN

Live Stream: ESPN App

Get more betting analysis and predictions at Sportsbook Wire.

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This article originally appeared on College Sports Wire: Louisville vs. Clemson: Week 12 College Football Betting Odds, Prediction

Reporting by Tyler Nettuno, College Sports Wire / College Sports Wire

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