All of Boyd's scoring throws came in the first half and went to five different receivers, as was the case last season when he threw for five touchdowns against North Carolina.
Clemson improved to 7-1 for the season and is 4-1 in the ACC's Atlantic Division, tied for the lead with Florida State. The Tigers have won four in a row since suffering a 49-37 setback to Florida State.
Wake Forest slipped to 4-4 for the campaign and is 2-4 in the Atlantic Division.
Clemson scored the game's first five touchdowns with Boyd hitting Brandon Ford on a 9-yard pass to open the scoring.
He then threw for four scores in the second period, the passes going to Sam Cooper for 12 yards, DeAndre Hopkins for 12, Charone Peake for two and Tommy Bohanon for eight.
D.J. Howard produced Clemson's only second-half touchdown on a 1-yard run in the fourth quarter.
Boyd completed 27-of-38 passes for 428 yards without an interception. He has 20 touchdowns for the season.
Tanner Price threw two touchdowns passes for the Demon Deacons, both to Tommy Bohanon. The first one came with 12 seconds left in the opening half.
Price was 27-of-44 for 232 yards.