Boyd went 20-of-27 passing, overcoming two interceptions and four sacks as the Tigers (5-0, 3-0 ACC) remained undefeated.
Sammy Watkins led Clemson's receiving corps with four grabs for 126 yards and a score while Adam Humphries scored twice on three catches for 118 yards.
Stanton Seckinger and Martavis Bryant chipped in one touchdown catch each.
The Orange (2-3, 0-1) fell in their first-ever ACC game as Terrel Hunt was held to 8-of-24 passing for 52 yards and three pick-offs.
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