Boyd was 27 of 38 and connected with Watkins for three plays of 50 or more yards, including a 61-yarder for a score.
Watkins finished with eight catches and Boyd added touchdown throws of 9 yards to Brandon Ford, 12 yards each to Sam Cooper and DeAndre Hopkins and 2 yards to Charone Peake.
The Tigers (7-1, 4-1 Atlantic Coast Conference) scored the first 35 points, including a four-touchdown second quarter, in their fourth consecutive victory and fourth in a row in the series with the Demon Deacons.
Five days after Virginia Tech held Clemson to season lows in every significant offensive statistic except the final score, the Tigers rolled up 534 total yards and essentially ended this one at halftime.
Boyd broke Charlie Whitehurst’s 10-year-old record of 420 yards passing after Watkins took care of the school’s receiving mark of 197 yards set in September by Hopkins against Boston College.
Tanner Price was 27 of 44 for 232 yards for Wake Forest (4-4, 2-4). He threw touchdown passes covering 8 and 18 yards to Tommy Bohanon.
The Deacons had minus-23 yards rushing in the first half. They’ve played two Top 25 teams and have been outscored 94-13 while allowing 1,146 total yards.
D.J. Howard added a late 1-yard touchdown run for Clemson, which was legitimately concerned after its lackluster 38-17 victory over the Hokies. In that game, the Tigers managed just 160 yards passing, 135 yards rushing and 295 total yards – a performance that left offensive coordinator Chad Morris vowing it wouldn’t happen again.
It certainly didn’t – at least, not during an overwhelming first half.
The defending ACC champions eclipsed last week’s yardage total by halftime, gaining 343 yards before the break.
Watkins, who sat out for the Tigers’ first three plays because he was three minutes late for a team meeting, got the offense rolling on its third possession. He slipped behind the Wake Forest secondary and Boyd found him down the left sideline for the 57-yard pass that set up his touchdown pass to Ford.
Watkins then made it 14-0 on the first play of the second quarter when he took a throw from Boyd near the sideline, shook off two tacklers and outran two more on his way to his first touchdown reception of the season.
Boyd, who also threw for five TDs last year in a home win against North Carolina, then hit Cooper with a scoring pass 6 minutes later, and by then, the Tigers were well on their way to their sixth win in seven meetings with Wake Forest.