No. 1: Miami Hurricanes (October 17th)
Louisville will travel to play the Miami Hurricanes next Friday night, and it will undoubtedly be the biggest game of the 2025 season for the Cardinals. After coming off that heartbreaking loss to Virginia last week, Louisville will have to take on one of the best teams in college football on a Friday night, and on the road in a hostile environment.
Louisville should have won against Virginia last week, and because of that, I wouldn't put it past Jeff Brohm to give Miami a scare. Every Louisville fan knows about the Brohm slip-up game, where he beats a top ten team and then proceeds to lose to a terrible team the following week. However, no one is discussing the inverse of that, which could happen as soon as next week in Miami.
Regardless of whether Louisville wins or not against Miami, the game next Friday night is the biggest of the season for the Cards. Louisville will have a chance to shake up the landscape of college football, and there isn't another game on its schedule that has the opportunity to do that.