Boyd completed 17-of-24 passes, including a 64-yard touchdown pass to Sammy Watkins on the third offensive play of the game, as the Tigers rolled up 573 yards of total offense in the one-sided affair.
Heisman Trophy-hopeful Boyd led three first-quarter touchdown drives within the first 7 1/2 minutes. He also keyed Clemson's ground attack, rushing 17 times en route to 69 yards and a touchdown.
Watkins finished with six receptions for 113 yards.
Wake Forest (2-3, 0-2) mustered only 125 passing yards from Tanner Price.