Boone completed 24-of-29 passes for 256 yards and hit Jamison Crowder for two scores.
The victory moved Duke (9-2, 5-2 ACC) to within one win of the ACC Coastal Division title and a date with Florida State in the conference championship game.
Wake Forest (4-7, 2-6) turned the ball over on its final two possessions in a scoreless fourth quarter and limped on to its fourth consecutive loss.
Tanner Price threw for 124 yards, including a touchdown, and ran for a score in the third quarter that put the Demon Deacons ahead 21-14. But Duke answered with a 58-yard TD catch by Crowder that tied the score and a 3-yard scoring run by Brandon Connette to close out the scoring with 3:21 left in the third quarter.
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