Louisville secured a historic victory over No. 11 Clemson, winning 33-21 and ending Clemson's 22-game home night winning streak. Freshman Isaac Brown was pivotal with 151 rushing yards and a decisive 45-yard touchdown, while Brock Travelstead contributed four field goals. Despite Clemson outgaining Louisville 450-366 and Phil Mafah's 199 total offensive yards, the Tigers struggled to convert yardage into points. The loss severely impacts Clemson’s ACC title and College Football Playoff prospects, now relying on other teams' results for a chance at the title. Furthermore, the defeat underscores a pattern for Clemson, who have lost three consecutive post-bye-week games.