Sep 27, 2025; Pittsburgh, Pennsylvania, USA; Louisville Cardinals running back Isaac Brown (1) runs the ball against the Pittsburgh Panthers during the first quarter at Acrisure Stadium. Mandatory Credit: Charles LeClaire-Imagn Images

We have a sneaky good matchup in the ACC on Saturday afternoon as Virginia looks to stay hot when it hits the road to take on Louisville.

The Cavaliers enter this one with momentum on their side, coming off a top-10 win at home in double overtime against Florida State. Now, they draw an unbeaten Louisville team that erased an early 17-point deficit to beat Pittsburgh on the road in its ACC opener last weekend.

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.

Stream Louisville vs. Virginia

Louisville vs. Virginia game odds

All college football odds via BetMGM

  • Spread: Louisville -7 (-105), Virginia +7 (-115)
  • Money line: Louisville -250, Virginia +200
  • Over/Under: Over 61.5 (-110), Under 61.5 (-110)

Louisville vs. Virginia prediction, pick:

The Cavaliers impressed in the win over Florida State, particularly the way they were able to run the ball effectively and take the ball away from the Seminoles. However, this does feel like a potential letdown spot. This is a tough matchup against the Cardinals and star running back Isaac Brown.

Miller Moss may give UVA an interception or two in this game, but it's hard to imagine Virginia can keep it up on the road against another quality ACC opponent.

Prediction: Louisville 34, Virginia 23

Best Bet: Louisville -7, Under 61.5

Louisville vs. Virginia channel, start time, streaming:

Time: 3:30 p.m. ET

TV: ESPN2

Live Stream: ESPN+

Get more betting analysis and predictions at Sportsbook Wire.

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This article originally appeared on College Sports Wire: Louisville vs. Virginia: Week 6 college football betting odds, prediction, pick

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

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