Boyd made good on 24-of-29 passes for 377 yards with three TDs and an interception. He also ran for a score as Clemson (8-1, 6-1 ACC) won for the fourth time in five meetings with Virginia.
Sammy Watkins caught a pair of scoring strikes en route to 169 yards on eight total receptions.
Roderick McDowell chipped in with a rushing score and a touchdown reception, racking up 107 total yards for the Tigers.
Virginia (2-7, 0-5) was paced by David Watford, who rushed for the Cavaliers' only TD while completing 16-of-35 passes for 130 yards with an interception.