3 must-win games that will make or break Louisville’s 2025 season

2. At Pittsburgh – Sept. 27

Pitt has been a consistent thorn in Louisville’s side. Since joining the ACC, the Cardinals are just 2–3 against the Panthers and 5–8 all-time on the road in the series. While the Panthers' season was a disaster, they still showed they can be a spoiler team in the ACC, and the Cardinals are getting them as their first ACC opponent in week 5.

The Panthers are going to be challenging, and last year they proved they can be a contender early in the season. The Cardinals blew them out last year, 37-9, but now with this game on the road and early in the season, Brohm's Cardinals will have a much bigger challenge.

This is Louisville’s first real test of the season, and don't be surprised if this game comes down to the fourth quarter. A win could set the tone for an ACC title run — while a loss might force the Cards to play catch-up the rest of the way. Louisville will be coming off three relatively cakewalk opponents, all from L&N Stadium, so with this being their first road test and first ACC matchup, it will be crucial for Louisville to walk away with a win.