Chris Thompson ran for 104 yards and two scores and James Wilder Jr. added two touchdowns runs for the Seminoles, who broke open a close game with 35 second-half points.
Florida State (4-0. 2-0 Atlantic Coast Conference) trailed until late in the third quarter, taking its first lead at 35-31 on Manuel's 29-yard touchdown pass to Rodney Smith. The Seminoles, who finished with 667 yards, built a 49-31 lead before Clemson scored late.
Clemson (3-1, 0-1) built a 28-14 lead early in the third quarter on a 52-yard pass from Sammy Watkins to Andre Ellington.
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