Two weeks of rest. Two weeks to get well. Two weeks to prepare for the home stretch of remaining undefeated in the ACC.

Maybe the Clemson Tigers should have just kept playing instead?

The No. 11 Tigers, who had one of the best offenses in the country, short-circuited a two-week layoff and fell 33-21 to Louisville on Saturday at Memorial Stadium.

Clemson (6-2, 5-1 in ACC) is no longer in control of its destiny to reach the ACC Championship Game. Both Miami and SMU won on Saturday and remained undefeated in ACC play. If the Hurricanes and Mustangs remain undefeated, they will meet in Charlotte in December.

The Tigers will need help because they couldn't help themselves against the Cardinals (6-3, 4-2), who played an exceptional game for the first time in program history and defeated Clemson.

A Clemson offense that averaged 42 points and 490 yards per game and 7.1 yards per play couldn't find much traction against the Cardinals' defense. Although the Tigers finished the game with 450 total yards, they were well below their season average, gaining just 4.5 yards per play.

While Clemson running back Phil Mafah finished the game with 171 yards and two touchdowns, Louisville's defense was clearly focused on giving Mafah a chance to gobble up all the yards he wanted.

Quarterback Cade Klubnik had his worst performance since the season-opening loss to Georgia. He threw for 228 yards with one touchdown.

The Tigers trailed 26-7 in the final 15 minutes and were unable to gain any ground. The quarter began with Louisville blocking Clemson kicker Nolan Hauser's second field goal attempt with 12:46 to play.

Clemson was unable to play with pace down the stretch as the Tigers were not allowed to operate in the middle of the field in the passing game and did not show much of a sense of urgency. Louisville's defense had two sacks and broke up five passes.

Clemson settled for short passes and Mafah runs and cashed in with a 3-yard touchdown run with six minutes to play. But it took five minutes to get there.

After the touchdown, Tigers coach Dabo Swinney opted to kick the extra point to cut the lead to 12. A successful two-point conversion would have cut the lead to 11 and allowed for a Clemson touchdown, a two-point conversion and a field goal to tie the game.

The Tigers took an onside kick and almost recovered, but Louisville was awarded the ball, causing the crowd to throw debris onto the turf. On the Cardinals' first play of the game, Isaac Brown sprinted 45 yards for a touchdown to put the game on ice.

Louisville quarterback Tyler Shough threw for 156 yards while Brown rushed for 151 yards. Shough also ran in for a touchdown. Clemson's defense gave up 366 yards, but Louisville managed 210 yards on the ground to control the game.

Clemson trailed at halftime for the first time since its season-opening loss to Georgia as Louisville took a 17-7 lead.

The Cardinals, trailing 7-3 in the second quarter, engineered a 92-yard drive to take a 10-7 lead with 5:42 left, capped by Shough's 4-yard touchdown run.

Then Louisville blocked a Hauser field goal to set up a drive that led to running back Keyjuan Brown's 1-yard touchdown run with 43 seconds left.

The Tigers' only score in the first half was a 12-yard touchdown pass from Klubnik to Antonio Williams that gave Clemson a 7-3 lead late in the first quarter.