The unbeaten Seminoles (9-0, 7-0 ACC) defense put two touchdowns on the board and held Wake Forest (4-6, 2-5) to a fourth-quarter field goal and 165 yards of total offense.
Wake Forest coughed up six turnovers, including an interception returned for a touchdown by Nate Andrews and a fumble recovery in the end zone by Jalen Ramsey.
James Wilder and Devonta Freeman ran for touchdowns for the Seminoles, who have scored at least 41 points in every game this season.
Tyler Cameron, the first of three quarterbacks employed by the Demon Deacons, completed 5-of-19 passes for 63 yards and was picked off three times. Josh Harris carried the ball 15 times for 63 yards, and Chad Hedlund put Wake on the board in the fourth quarter with a 23-yard field goal.