Cullen Harper completed 20 of 28 passes for 262 yards and two touchdowns for the 23rd-ranked Tigers (2-1, 1-0 ACC). C.J. Spiller rushed 10 times for 61 yards and one TD, and also caught four balls for 35 yards and another score.
Jacoby Ford caught six of Harper's tosses for 106 yards and a touchdown.
For North Carolina State (1-2, 0-1 ACC), Russell Wilson and Harris Beck combined for 15 of 29 passing for 152 yards and two interceptions. Andre Brown ran for 64 yards on 14 carries and caught four passes for 51 yards.
Nate Irving scored the Wolfpack's only touchdown seven seconds into the game, picking off Harper on the first play from scrimmage and running 33 yards for a TD. The extra point was blocked.
Clemson scored on its next possession and never trailed.
Mark Buchholz kicked a 22-yard field goal for Clemson and Josh Czajkowski nailed a 22-yarder for N.C. State.
Clemson racked up 428 yards of offense to the Wolfpack's 288.