Duke (19-3, 10-1 Atlantic Coast Conference) then went on a 12-2 run in the last 3:28 of the opening period, and followed that with a 15-2 run the first 4:37 of the second half. The Blue Devils hit 13 of 25 second-half field-goal attempts to win going away, 80-55.
"They picked up their defensive intensity, and we had some mental let-downs and that was pretty much the ball game right there in that stretch at the end of the first half and the start of the second," Wake Forest's Charlene Curtis said.
Alana Beard scored 23 points, and Iciss Tillis had 22 points, seven rebounds and four blocks for Duke. The duo had eight points each during the decisive run that gave the Blue Devils a 54-27 lead.
Lindsey Harding added 10 points and eight assists for Duke, which beat Wake Forest for the 25th straight time.
Tillis played for the first time since suffering a concussion Feb. 4 and missing two contests.
"It felt good to be back," she said. "You never realize how much you miss the game until you can't play."
The Demon Deacons (10-13, 3-9) lost their fourth straight conference game. They missed seven of their last eight shots of the first half and finished a season-worst 30.6 percent (19-for-62).
Ferrell led Wake Forest with 17 points, and Elizabeth Strunk had 15.
The Blue Devils had a school-record 14 blocks.
"We usually don't go for that many blocks," Duke coach Gail Goestenkors said. "We usually take more charges. We blocked shots, but they got a lot of offensive rebounds.
"We allowed 11 offensive rebounds. That's where the real frustration was."
Goestenkors said Duke is concerned with rebounding because it faces No. 15 North Carolina on Saturday. The Tar Heels lead the ACC with 44.2 rebounds a game, while Duke leads in rebounding margin (plus-9.7 a game) and blocks (6.48).
"I don't know about the blocks, but Duke played excellent defense," Curtis said. "That's what makes good teams good. That's what good teams do to you. They get steals and then make baskets in transition."
Duke scored 20 points off 18 Wake Forest turnovers. That helped the Blue Devils score 44 points in the paint and shoot 28-for-56 (50 percent) from the field.
"That was the difference," Curtis said. "We started being careless with the ball, and they were stepping in the passing lanes or taking the ball out of our hands."