Matchup Preview and Final Score Prediction For No. 24 Virginia vs Louisville

Can the Hoos follow up their Florida State upset with another ACC statement?

Sep 26, 2025; Charlottesville, Virginia, USA; Virginia Cavaliers quarterback Chandler Morris (4) passes the ball as Florida State Seminoles defensive lineman Darrell Jackson Jr. (6) chases at Scott Stadium. Mandatory Credit: Geoff Burke-Imagn Images | Geoff Burke-Imagn Images

Virginia (4–1, 1–0 ACC) stunned the college football world last Friday night by knocking off No. 8 Florida State, their first ranked win since 2019. Now, the Cavaliers enter the AP Top 25 and head to Louisville for their biggest road test yet. A win would not only cement UVA as an ACC contender but also mark Tony Elliott’s first signature road victory as head coach.

Louisville (4–0, 2–0 ACC) survived a scare at Pittsburgh, rallying in the fourth quarter behind quarterback Miller Moss for a 34–27 win. The Cardinals are unbeaten at home under Jeff Brohm and enter Saturday’s game as favorites. History suggests it will be tight—four of the last six meetings between UVA and Louisville have been decided by one score.

Virginia Offense vs. Louisville Defense

Chandler Morris comes in hot after accounting for five total touchdowns against FSU, earning ACC Player of the Week honors. The senior quarterback has quickly become the centerpiece of Virginia’s rebuild, throwing for 229 yards and rushing for three more scores in the upset.

He’s supported by one of the deepest backfields in the conference. J’Mari Taylor carried the ball 27 times for 99 yards and a touchdown last week, while Harrison Waylee and Xavier Brown continue to rotate in for explosive plays. With Noah Vaughn sidelined by injury, the trio will again share the workload.

Sep 26, 2025; Charlottesville, Virginia, USA; Virginia Cavaliers running back J'Mari Taylor (3) carries the ball as Florida State Seminoles defensive back Ja'Bril Rawls (11) tackleds in the second overtime at Scott Stadium. Mandatory Credit: Geoff Burke-Imagn Images | Geoff Burke-Imagn Images

Up front, injuries have forced adjustments. Center Brady Wilson remains out, so veteran Drake Metcalf shifts inside with Kevin Wigenton II filling at guard. The key matchup comes at tackle, where McKale Boley faces off with Louisville’s Clev Lubin, who leads the Cards with 3.5 sacks. If Morris gets time, he has a diverse receiver corps led by Jahmal Edrine, Trell Harris, and slot target Cam Ross, plus Dakota Twitty emerging at tight end.

Louisville Offense vs. Virginia Defense

Louisville’s attack flows through Miller Moss. The USC transfer passed for 339 yards and three touchdowns in the Pitt win, leaning heavily on wideout Chris Bell (10 catches, 135 yards, one score). The run game has been less efficient—Duke Watson was limited to 47 yards on 14 carries—but the Cards use tempo and spacing to open passing lanes.

Virginia’s defense showed resilience against FSU but also gave up chunk runs. Elliott noted the safeties need better pursuit angles to clean up those leaks. Still, the front seven can cause problems. Jahmeer Carter anchors the middle, Mitchell Melton brings pressure off the edge, and linebacker Kam Robinson continues to be a force against the run.

Sep 26, 2025; Charlottesville, Virginia, USA; Virginia Cavaliers defensive back Ja'son Prevard (10) makes a game winning interception in the end zone on a pass intended for Florida State Seminoles wide receiver Squirrel White (4) in the second overtime period at Scott Stadium. Mandatory Credit: Geoff Burke-Imagn Images | Geoff Burke-Imagn Images

Turnovers could swing this matchup—Ja’son Prevard’s game-winning interception against Florida State was proof of how opportunistic the secondary can be.

Odds for Virginia vs. Louisville

Provided by Fanduel Sportsbook (as of Friday morning):

• Moneyline: Louisville -234 | Virginia +194
• Spread: Louisville -6.5 | Virginia +6.5
• Over/Under: 61.5

Louisville is 4–0 as a favorite but just 0–3 ATS when laying more than a touchdown. Virginia is 4–1 ATS this season, including a cover and outright win as a 6.5-point underdog last week.

Keys for Virginia’s Victory

• Pressure Miller Moss – Disrupting his rhythm is essential. UVA’s front must collapse the pocket and force mistakes.

• Use the Run Game – Taylor, Brown, and Waylee give Virginia reliability, explosiveness, and balance. Sustaining drives on the ground will help neutralize Louisville’s pass rush as well as limiting interceptions on the scramble.

• Limit Explosive Plays – The Cavaliers can’t afford busted coverages. Keeping everything in front of them will be critical to slowing the Cards. The secondary needs to come up big.

The Final Outlook

Louisville is unbeaten, at home, and backed by one of the ACC’s most efficient quarterbacks. Virginia arrives with confidence, momentum, and a chance to prove last week wasn’t a fluke. Expect another close game—just as history between these two suggests.

Prediction: Louisville 33, Virginia 28. The Hoos keep it tight, but the Cardinals’ passing game makes the difference late.

Game odds refresh periodically and are subject to change. If you or someone you know has a gambling problem and wants help, call 1-800-GAMBLER.