Chris Thompson ran for 147 yards and a touchdown and Dustin Hopkins kicked four field goals for the No. 23 Seminoles (10-4), who reached 10 wins for the first time since 2003.
Manuel took over for senior quarterback Christian Ponder, who left early in the second quarter with a concussion. No. 19 South Carolina lost running back Marcus Lattimore when he was hit hard on the Gamecocks' first drive.
South Carolina (9-5), which was seeking its first 10-win season since 1984, committed five turnovers. Stephen Garcia threw three first-half interceptions and Lattimore and Alshon Jeffery lost fumbles to leave the Gamecocks trailing 16-3 in the third quarter.
Garcia recovered to lead two long touchdown drives that trimmed Florida State's lead to 19-17 before Manuel answered with the 7-yard scoring pass to Taiwan Easterling.
Florida State cornerback Greg Reid, whose hits caused the fumbles by Lattimore and Jeffery, deflected a fourth-down pass by Garcia with 3:23 remaining.
Garcia completed 19 of 34 passes for 243 yards and also scored on a nifty play in the third. On a third-down play from the Florida State 3, Garcia threw a screen pass to Ace Sanders, who threw back across the field to Garcia alone in the right side of the end zone.
The Seminoles answered with Hopkins' fourth field goal, from 45 yards, to push the lead to nine.
Garcia responded by leading a 79-yard drive, capped by Brian Maddox's 7-yard TD run that made it 19-17. Garcia helped set up the score with a 29-yard pass to Jeffery.
South Carolina quarterback Stephen Garcia (5) is stopped by Florida State safety Nick Moody (10) in the second quarter of the Chick-fil-A Bowl NCAA college football game on Friday, Dec. 31, 2010, in Atlanta. (AP Photo/John Amis)
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