TALLAHASSEE, Fla. — EJ Manuel threw for a career-high 380 yards and two touchdowns and ran for another 102 yards as fourth-ranked Florida State rallied from a two-touchdown deficit to defeat No. 10 Clemson 49-37 on Saturday night.

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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  • Chris Watt, Manti Te'o, TJ Jones

    Notre Dame's Chris Watt (66), Manti Te'o (5) and TJ Jones (7) celebrate with fans after Notre Dame defeated Michigan, 13-6, in an NCAA college football game Saturday, Sept. 22, 2012, in South Bend, Ind. (AP Photo/Darron Cummings)

  • Charlie Strong

    Louisville head coach Charlie Strong, right, shouts during the second half of an NCAA college football game against Florida International in Miami, Saturday, Sept. 22, 2012. Louisville defeated FIU 28-21. (AP Photo/Lynne Sladky)

  • Eric Reid

    LSU safety Eric Reid (1) reacts after LSU recovered an Auburn fumble in the second half of an NCAA college football game Saturday, Sept. 22, 2012 at Jordan-Hare Stadium in Auburn, Ala. LSU beat Auburn 12-10. (AP Photo/Dave Martin)

  • Weber State's Jordan Clemente (5) gets tripped up by Eastern Washington's Ronnie Hamlin (39) during an NCAA college football game in Ogden, Utah, on Saturday, Sept. 22, 2012. (P Photo/Standard-Examiner, Nicholas Draney) TV OUT LOCAL TV OUT MANDATORY CREDIT

  • C.J. Bennett

    South Alabama quarterback C.J. Bennett (15) looks for an open receiver in the third quarter of their NCAA college football game against Mississippi State in Starkville, Miss., Saturday, Sept. 22, 2012. No. 23 Mississippi State won 30-10. (AP Photo/Rogelio V. Solis)

  • Manti Te'o

    Notre Dame's Manti Te'o (5) reacts after Notre Dame defeated Michigan, 13-6, in an NCAA college football game, Saturday, Sept. 22, 2012, in South Bend, Ind. (AP Photo/Darron Cummings)

  • John Hubert

    Kansas State running back John Hubert (33) celebrates with fans following a 24-19 victory over Oklahoma in an NCAA college football game in Norman, Okla., Saturday, Sept. 22, 2012. (AP Photo/Sue Ogrocki)

  • Michael Buchanan Colby Cameron

    Illinois defensive lineman Michael Buchanan sacks Louisiana Tech quarterback Colby Cameron (10) during the first half of an NCAA college football game Saturday, Sept. 22, 2012 in Champaign, Ill. Louisiana Tech defeated Illinois 52-24. (AP Photo/Seth Perlman)

  • Manti Te'o

    Notre Dame's Manti Te'o reacts following a tackle during the second half against Michigan during an NCAA college football game on Saturday, Sept. 22, 2012, in South Bend, Ind. Notre Dame defeated Michigan 13-6. (AP Photo/Darron Cummings)

  • James Wilder Jr., Bashaud Breeland

    Florida State running back James Wilder Jr. (32) stiff-arms Clemson cornerback Bashaud Breeland (17) on a 35-yard run during the fourth quarter of an NCAA college football game on Saturday, Sept. 22, 2012, in Tallahassee, Fla. (AP Photo/Phil Sears)

  • Sione Tuihalamaka, Stetzon Bair

    Arizona defender Sione Tuihalamaka, left, celebrates Stetzon Bair's interception during the first half of their NCAA college football game against Oregon in Eugene, Ore., Saturday, Sept. 22, 2012. (AP Photo/Don Ryan)

  • Donnell Kirkwood, Ed Olson, Mike Henry

    Minnesota running back Donnell Kirkwood celebrates with teammates Ed Olson (58) and Mike Henry, right, after Kirkwood's rushing touchdown in the second half of an NCAA college football game against Syracuse in Minneapolis on Saturday, Sept. 22, 2012. Minnesota defeated Syracuse 17-10. (AP Photo/Andy King)

  • Collin Klein

    Kansas State quarterback Collin Klein carries for a touchdown against Oklahoma in the fourth quarter of an NCAA college football game in Norman, Okla., Saturday, Sept. 22, 2012. Kansas State won 24-19. (AP Photo/Sue Ogrocki)

  • Aaron Murray

    Georgia quarterback Aaron Murray (11) calls signals against Vanderbilt during the second quarter of an NCAA college football game, Saturday, Sept. 22, 2012, in Athens, Ga. (AP Photo/John Amis)

  • New Mexico's Jhurell Pressley makes a touchdown against New Mexico State during an NCAA college football game Saturday, Sept. 22, 2012, in Las Cruces, N.M. (AP PHOTO/Las Cruces Sun-News, Robin Zielinski)

  • Tennessee wide receiver Justin Hunter (11) celebrates with wide receiver Cordarrelle Patterson (84) after a touchdown during the second half of an NCAA college football game against Akron on Saturday, Sept. 22, 2012, in Knoxville, Tenn. (AP Photo/Knoxville News Sentinel, Amy Smotherman Burgess)

  • Georgia fans cheer the team before Georgia and Vanderbilt kicked off in an NCAA college football game, Saturday, Sept. 22, 2012, in Athens, Ga. (AP photo/John Amis)

  • Travis Tannahill, Javon Harris, Demontre Hurst

    Kansas State tight end Travis Tannahill (80) is tackled by Oklahoma's Javon Harris (30) and Demontre Hurst (6) during the fourth quarter of an NCAA college football game in Norman, Okla., Saturday, Sept. 22, 2012. Kansas State won 24-19. (AP Photo/Sue Ogrocki)

  • Ryan Nassib, D.L. Wilhite

    Syracuse quarterback Ryan Nassib, right, is sacked by Minnesota's D.L. Wilhite in the first half of an NCAA college football game in Minneapolis, Saturday, Sept. 22, 2012. (AP Photo/Andy King)

  • Cody Getz,

    Air Force Academy's Cody Getz (28) gets gang tackled by the UNLV defense during the first half of their NCAA college football game in Las Vegas on Saturday, Sept. 22, 2012. (AP Photo/Las Vegas Review-Journal, Jason Bean)

  • Jimbo Fisher, Dabo Swinney

    Florida State coach Jimbo Fisher, left, and Clemson coach Dabo Swinney meet after an NCAA college football game on Saturday, Sept. 22, 2012, in Tallahassee, Fla. Florida State won 49-37. (AP Photo/Phil Sears)

  • Montana State's quarterback DeNarius McGhee runs the ball against Northern Colorado during the second half of their NCAA Big Sky Conference football game on Saturday, Sept. 22, 2012 in Bozeman, Mont. Montana State defeated Northern Colorado 41-16. (AP Photo/Bozeman Daily Chronicle, Adrian Sanchez-Gonzalez)

  • Minnesota student fans cheer during the second half of an NCAA college football game against Syracuse in Minneapolis, Saturday Sept. 22, 2012. Minnesota defeated Syracuse 17-10. (AP Photo/Andy King)

  • Montana State's wide receiver Tanner Bleskin, left, takes a hit from Northern Colorado's Mykel Morse during the first half of their NCAA Big Sky Conference football game on Saturday, Sept. 22, 2012 in Bozeman, Mont. Montana State defeated Northern Colorado 41-16. (AP Photo/Bozeman Daily Chronicle, Adrian Sanchez-Gonzalez)

  • Menelik Watson

    Florida State tackle Menelik Watson (71) celebrates in the third quarter of an NCAA college football game against Clemson on Saturday, Sept. 22, 2012, in Tallahassee, Fla. Florida State won 49-37. (AP Photo/Phil Sears)

  • Taylor Kelly

    Arizona State quarterback Taylor Kelly, left, looks for an open receiver against Utah in the second quarter of an NCAA college football game Saturday, Sept. 22, 2012, in Tempe, Ariz. (AP Photo/Paul Connors)

  • The Minnesota marching band takes the field before an NCAA football game between Minnesota and Syracuse in Minneapolis, Saturday, Sept. 22, 2012. Minnesota defeated Syracuse 17-10. (AP Photo/Andy King)

  • Marcus Mariota

    Oregon quarterback Marcus Mariota unleashes a pass during the first half of their NCAA college football game against Arizona in Eugene, Ore., Saturday, Sept. 22, 2012. (AP Photo/Don Ryan)

  • Michael Carter, Jarrod West

    Minnesota cornerback Michael Carter, right, interferes with Syracuse wide receiver Jarrod West in the second half of NCAA football in Minneapolis, Saturday, Sept. 22, 2012. Minnesota defeated Syracuse 17-10. (AP Photo/Andy King)

  • Perry Jones, Chris Hackett, Kenny Cain

    Virginia running back Perry Jones (33) is upended by TCU safety Chris Hackett (1) as linebacker Kenny Cain (51) looks on during the first half on an NCAA college football game Saturday, Sept. 22, 2012, in Fort Worth, Texas. (AP Photo/LM Otero)

  • Braxton Miller, Jake Genus, Lamar Johnson

    Ohio State's Braxton Miller, left, scores a touchdown against Alabama-Birmingham's Jake Genus, bottom, and Lamar Johnson (6) during the second quarter of an NCAA college football game Saturday, Sept. 22, 2012, in Columbus, Ohio. (AP Photo/Jay LaPrete)

  • Ryan Radcliff

    Central Michigan quarterback Ryan Radcliff throws a pass during the first half of an NCAA college football game against Iowa, Saturday, Sept. 22, 2012, in Iowa City, Iowa. (AP Photo/Charlie Neibergall)

  • Casey Pachall, Trevone Boykin

    TCU quarterback Casey Pachall (4) celebrates a touchdown with teammate Trevone Boykin during the first half on an NCAA college football game against Virginia, Saturday, Sept. 22, 2012, in Fort Worth, Texas. (AP Photo/LM Otero)

  • Melvin Gordon, DeShawn Grayson

    Wisconsin running back Melvin Gordon (25) runs over UTEP defensive back DeShawn Grayson during the first half of a NCAA college football game, Saturday, Sept. 22, 2012, in Madison, Wis. (AP Photo/Andy Manis)

  • Travis Howard, Jackie Williams

    Ohio State's Travis Howard, right, tackles UAB's Jackie Williams during the second quarter of an NCAA college football game Saturday, Sept. 22, 2012, in Columbus, Ohio. (AP Photo/Jay LaPrete)

  • David Jenkins

    Fans reach to touch TCU cornerback David Jenkins (26) as he runs onto the field before an NCAA college football game against Virginia Saturday, Sept. 22, 2012, in Fort Worth, Texas. (AP Photo/LM Otero)

  • Ja-Mes Logan, Vince Sanders

    Mississippi wide receiver Ja-Mes Logan (85) celebrates his touchdown with Mississippi wide receiver Vince Sanders (10) in the first half of an NCAA college football game in New Orleans, Saturday, Sept. 22, 2012. (AP Photo/Bill Haber)

  • Jason Wilson, Keenan Davis

    Central Michigan defensive back Jason Wilson, right, breaks up a pass intended for Iowa wide receiver Keenan Davis during the first half of an NCAA college football game, Saturday, Sept. 22, 2012, in Iowa City, Iowa. (AP Photo/Charlie Neibergall)

  • Maryland West Virginia Football

    West Virginia wide receiver Tavon Austin (1) carries a pass in for a touchdown during an NCAA college football game against Maryland in Morgantown, W.Va., Saturday, Sept. 22, 2012. (AP Photo/Christopher Jackson)

  • Jared Abbrederis, Nick Lamaison

    Wisconsin linebacker Chris Borland, top, blocks a pass by UTEP quarterback Nick Lamaison (7) during the first half of an NCAA college football game Saturday, Sept. 22, 2012, in Madison, Wis. (AP Photo/Andy Manis)

  • A Tulane players carries the jersey of safety Devon Walker, who fractured his spine in a Sept. 8 game at Tulsa, onto the field before the start of an NCAA college football game against Mississippi in New Orleans, Saturday, Sept. 22, 2012. (AP Photo/Bill Haber)

  • Dyrell Roberts, Darrell Hunter

    Virginia Tech split end Dyrell Roberts (11) hauls in a touchdown pass against Bowling Green defensive back Darrell Hunter during the first half of an NCAA college football game Saturday, Sept. 22, 2012 at Lane Stadium, in Blacksburg, Va. (AP Photo/Don Petersen)

  • C.J. Johnson, Devin Powell

    Mississippi defensive end C.J. Johnson (10) knocks the ball from Tulane quarterback Devin Powell (1) during the first half of an NCAA college football game in Saturday, Sept. 22, 2012. in New Orleans. (AP Photo/Bill Haber)

  • Morgan Newton, Jon Bostic

    Kentucky quarterback Morgan Newton (12) throws a pass just before getting hit by Florida linebacker Jon Bostic (1) during the first half of an NCAA college football game, Saturday, Sept. 22, 2012, in Gainesville, Fla. (AP Photo/John Raoux)

  • Tevin Reese, Jemarcus Johnson

    Baylor wide receiver Tevin Reese, left, walks off the field with teammate Jemarcus Johnson, right, following their NCAA college football game, against Louisiana-Monroe, Friday, Sept. 21, 2012 in Monroe, Louisiana. Baylor won 47-42. (AP Photo/Waco Tribune Herald, Duane A. Laverty)