No. 11 Clemson lost its first ACC game of the season, falling 33–21 at home to Louisville. The win is the first for the Cardinals over the Tigers since joining the conference in 2014. Louisville had lost its previous eight meetings versus Clemson.

Isaac Brown ran for a 45-yard touchdown after the Cardinals recovered an onside kick attempt by Clemson to put the game away with 5:50 remaining in the game.

After Clemson running back Phil Mafah scored a 3-yard TD to make it a 26-13 game, Clemson opted to kick an extra point rather than attempt a two-point conversion to cut the margin to 11 points. That decision made more sense when the Tigers attempted an onside kick, but Louisville made the recovery. (Replay appeared to show that Clemson had two players offside anyway, but that didn't matter.)

Fans threw objects onto the field to protest but after the brief delay, Brown applied the dagger with his touchdown run.

The Tigers' passing game had no answer for Louisville's defense. Quarterback Cade Klubnik completed 33-of-56 passes for 228 yards and a touchdown, but most of that yardage came after the game was out of reach.

Mafah had a monster performance running the ball, gaining 171 yards on 30 carries, but his two touchdowns came too late. (Klubnik added 43 yards on 12 rushes.)

After falling behind 26-7, the Tigers needed to throw the ball to catch up. Yet Clemson and offensive coordinator Garrett Riley didn't show much urgency increasing the tempo and attempting to score faster.

Brown finished with 151 yards rushing on 20 carries for Louisville, with Chris Bell adding 47 yards on his lone rush. Quarterback Tyler Shough threw for 156 yards, completing 17 of 32 passes. Ja'Corey Brooks led the Cardinals in receiving with 42 yards on four receptions. And Brock Travelstead kicked four field goals, his longest for 49 yards.

With the loss, Clemson drops to third in the ACC behind Miami and SMU, which are both 5-0. Pittsburgh is right behind the Tigers at 3-1 after losing to SMU for its first conference defeat.