The Seminoles (3-0, 1-0 ACC) racked up 612 yards of total offense and held Wake Forest (2-1, 1-1 ACC) to 126 total yards and a rushing average of 1.2 yards per carry.
Thompson broke for touchdown runs of 74 and 80 yards in the second quarter as Florida State built up a 38-0 halftime lead before turning the game over to the bench.
Kenny Shaw and Rodney Smith caught TD passes and EJ Manuel was 15-of-24 passing for 176 yards.
Tanner Price was 8-of-22 for 82 for the Demon Deacons. Sherman Ragland had two catches for 48 yards.