Louisville vs Pittsburgh Picks and Predictions for Saturday, September 27, 2025

By: David Anicetti Updated 09/27/2025, 01:31 AM ET

The Louisville Cardinals visit the Pittsburgh Panthers at Acrisure Stadium on Saturday, September 27, 2025, at 12:00 p.m. ET. Louisville is 3–0 and won its most recent game 40–17 against Bowling Green. Pittsburgh is 2–1 and lost its most recent game 31–24 in overtime at West Virginia. Get more winners and fewer bad beats with our free college football predictions.

Louisville Preview

Louisville QB Miller Moss has 690 passing yards with 2 touchdowns and 2 interceptions. The ground game is Louisville’s strength. Isaac Brown has 248 rushing yards and 3 touchdowns, and Keyjuan Brown adds 110 yards and 3 touchdowns. Chris Bell leads the receivers with 197 yards and 1 score, while Caullin Lacy has 171 yards to stretch the field.

On defense, Clev Lubin has 19 tackles and 3.5 sacks, and Wesley Bailey adds additional strength up front against the run and pass. D’Angelo Hutchinson has an interception. In the kicking game, Cooper Ranvier is perfect at 6-for-6 on field goals with a long of 48, which helps when drives are stalled.

Pittsburgh Preview

Pittsburgh QB Eli Holstein has 822 passing yards with 9 touchdowns and 3 interceptions. Raphael Williams Jr. is the top target with 245 yards and 3 touchdowns, with Bryce Yates and Kenny Johnson are additional targets for Holstein. Desmond Reid leads all running backs with 142 rushing yards and 1 score.

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The defense is built around speed and pressure. Rasheem Biles has 29 tackles, and Kyle Louis has 2 sacks and an interception. Pitt has generated steady pressure so far, but the offense has allowed 8 sacks, so protection is a key point. The Panthers cannot allow quarterback sacks and on defense must pressure each time Louisville passes.

Louisville vs Pittsburgh Prediction

Louisville brings a steady run game and a strong rush on defense. Pitt can answer with big plays in the air, but Louisville’s front can disrupt timing and take Holstein out of his comfort zone. With Moss limiting mistakes and the Cardinals' running backs moving the chains, Louisville has the advantage on the road. Final Score Prediction: Louisville Cardinals win and cover ATS 30–20.