Louisville Cardinals running back Isaac Brown (1) scores a big fourth quarter touchdown against James Madison during the Cards' second college football game Friday September 5, 2025 at L&N Credit Union Stadium in Louisville, Kentucky. The Cards beat the Dukes 28-14.

It will be a fascinating early season ACC matchup at Acrisure Stadium in Pittsburgh on Saturday afternoon.

The unbeaten Louisville Cardinals travel to face a Pittsburgh Panthers team that is looking to bounce back from a tough overtime loss to rival West Virginia in the Backyard Brawl two weeks ago. Pitt will hope the bye week helped fix its passing game, which was fairly inefficient with Eli Holstein at quarterback in its loss to the Mountaineers.

The Panthers' defense will have its hands full with the Cardinals' run game. Running back Isaac Brown is averaging 13.1 yards per carry this year, more than any player in college football with as many touches. That's certainly a bit concerning for a Pittsburgh defense that allowed 174 yards on the ground in the loss to WVU.

Stream Pittsburgh vs. Louisville

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

Pittsburgh vs. Louisville game odds

All college football odds via BetMGM

  • Spread: Louisville -4.5 (-105), Pitt +4.5 (-115)
  • Money line: Louisville -190, Pitt +155
  • Over/Under: Over 57 1/2 (-110), Under 57 1/2 (-110)

Pittsburgh vs. Louisville prediction, pick:

Pitt looks like a flawed team so far, especially given its loss to a West Virginia team that has otherwise struggled. Louisville, meanwhile, looks like a potentially sneaky ACC contender, but it's hard to declare the Cardinals as such, given this team's toughest test came in a fairly sluggish win over James Madison.

Louisville may not be quite as good as some think, but we've seen enough to say that the Panthers have issues.

Prediction: Louisville 34, Pittsburgh 24

Best Bet: Louisville -4.5, Over 57 1/2

Pittsburgh vs. Louisville channel, start time, streaming:

Time: Noon ET

TV Channel: ESPN2

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: Pittsburgh vs. Louisville: Week 5 college football betting odds, prediction, pick

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

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