Pitt Panthers vs. Louisville Cardinals 2025 Preview: Must-Know Keys

It’s a Pitt Panthers vs. Louisville Cardinals matchup in 2025, as Week 5 is a preview of Pittsburgh’s ACC schedule. Pitt comes in at 2-1, while Louisville is a perfect 3-0 entering Acrisure Stadium this weekend.

Last week, the Panthers collapsed in Morgantown. They blew a 10-point lead in the fourth quarter, eventually losing 31-24 in overtime. Eli Holstein missed multiple open receivers, and also threw another red zone interception. It was one of the worst losses in the Pat Narduzzi era, and it’s looking like a disappointing season is on the horizon.

Can Pitt bounce back at home and start 1-0 in ACC play?

Pitt Panthers vs. Louisville Cardinals: Matchup History

As former Big East opponents, Pitt and Louisville have played 21 times since 1976. Pitt  currently leads the series 11-10. More recently, Pitt is 5-3 since 2010. However, Louisville did take last year’s matchup in dominant fashion, winning 37-9.

Since the ACC recently did away with divisions, you should expect to see these teams face off more often in the future.

The last time the two played at Acrisure Stadium was in 2023, when a 1-4 Pitt team took down the undefeated No. 14 Louisville, who was 6-0 entering that game.

Pitt vs. Louisville 2025 Preview: Keys to the Game and Predictions

Key Players for Louisville

Running back Isaac Brown has been a world-beater for the Cardinals this year. In limited action through the first three games, Brown has 19 carries for 248 yards and three touchdowns. That is good for an unbelievable 13.1 yards per carry. However, he does come up as questionable in this week’s injury report with an undisclosed injury. Him not playing would be a massive blow for the Louisville offense, and might be the sole reason they could lose this game.

As if things weren’t already bad with Brown questionable, their other star running back from last year, Duke Watson, is also questionable. Watson was out last week in the win against Bowling Green, and Brown left early after an 18 yard run in the first quarter. So the two key stars on offense are both questionable for Saturday.

On defense, lineman Clev Lubin has stood out for Louisville this year. Lubin leads the team in tackles and sacks with 11 and 3.5 respectively. It’s safe to say that he is on pace for an All-ACC season. Lubin will be poised with stopping what has already been a shaky run game of the Panthers. Neither of Desmond Reid or Juelz Goff have been that impressive outside of a couple plays this season, to the surprise of many.

Key Players for Pitt

If you didn’t think Desmond Reid was Pitt’s most important player on offense, you definitely do after Saturday. After Reid left the game in Morgantown, Pitt’s rushing attack was non-existent. This left more pressure on Eli Holstein, which lead to more bad throws, and more mistakes. Reid is listed as questionable with a “lower body injury”. If Reid doesn’t play, don’t be surprised if the spread, which is at Louisville -4.5 currently, gets near a touchdown.

Cataurus “Blue” Hicks has been a pleasant surprise for Pitt at receiver so far this year. He only has seven receptions in the early going, but he will have extra motivation this week. Hicks is a transfer from Louisville, and did not get much action there last year. Outside of the opener against Duquesne, Hicks has not been relevant. Expect Eli Holstein to try to get Hicks involved early and often.

Game Prediction

This is a weird spot for both teams. Louisville has not faced a Power 4 opponent yet. Meanwhile, Pitt is coming off a heart-breaking loss in Morgantown. It is a pivotal matchup in a crowded ACC in 2025. With Florida State and Miami being the clear top dogs so far, a win from either side in this game sets them up nicely for the rest of the season.

Louisville is lead by their rushing attack. Normally, Pitt’s strength is their run defense. However, it looked a little concerning last week against West Virginia. If Louisville exploits Pitt on the ground, they will win by multiple possessions.

For Pitt, their way to win will be to outscore Louisville. More specifically, the Panthers need Eli Holstein play mistake-free football. An average performance from the defense will mean Pitt will have to score at least three touchdowns to win, which is something they did not do last week. Expect this game to be close, but Louisville’s rushing attack may wear down the Pitt defense in the second half, control the clock, and win the game on the road.

Score Prediction: Louisville 31, Pitt 23