The University of Louisville gave up 21 third-quarter points and twice lost the lead on the road at Florida State in a 41-21 loss on Staurday afternoon before 71,225 fans.
The Cardinals led 7-6 at halftime and 14-13 with 9:08 left in the third quarter.
But the defense couldn't stop the Seminoles in the second half and Florida State won its 28th consecutive game against ACC foes and 18th straight game at home.
Lamar Jackson led the Cardinals with a career-high 307 yards passing and three touchdowns, while James Quick caught five passes for 130 yards and three TDs. The Cardinals rushed for just 99 yards.
Florida State is now 6-0 and Louisville is 2-4 with Boston College at home next Saturday at 12:30 p.m.