Boyd completed 12-of-21 passes for 160 yards and ran in a pair of 1-yard scores to extend Clemson's (6-1, 3-1 ACC) home winning streak to 11 games.
DeAndre Hopkins caught three passes for 68 yards and a touchdown. Andre Ellington led the Tigers on the ground with 96 yards and a 12-yard touchdown.
Jonathan Meeks intercepted two passes, including one he ran back 74 yards for a TD that gave Clemson a 24-10 lead early in the third quarter.
Logan Thomas completed 15-of-28 passes for 207 yards and ran 19 yards for a score for the Hokies (4-4, 2-2), who have not beaten Clemson since 2007.
Corey Fuller caught a touchdown pass and Cody Journell kicked a 40-yard field goal in the closing seconds of the first half.