The senior sure looked on top of her game Saturday.
Brittany Hunter had 12 points for the top-seeded Blue Devils (25-3), who are trying to win an unprecedented fifth straight tournament title. Mistie Bass added 10 points.
Tillis went 9-for-14 and had five rebounds, allowing the Blue Devils to overcome an off night by All-America Alana Beard. Beard, who averages nearly 21 points, scored nine on 4-for-12 shooting.
Tonia Brown had 23 points and 12 rebounds to lead the Demon Deacons (12-17).
"This was a really good game for us to open with because it was a tough matchup and I thought they came ready to play," Duke coach Gail Goestenkors said.
Duke started sluggishly, missing 13 of its first 16 shots and falling behind by eight points against the ninth-seeded Demon Deacons, who beat No. 8 seed Georgia Tech in Friday's play-in game. But the Blue Devils finally found some defensive intensity, forcing turnovers and getting out in transition for 15-0 run.
The Blue Devils scored 29 points off 26 turnovers and held the Demon Deacons to 34 percent shooting for the game.
Tillis had averaged 14 points per game over the last two seasons, but came into Saturday's game averaging just 11.8 points and shooting 40 percent. Those numbers could be blamed partly on a six-game stretch in January when Tillis scored just 34 points on 13-for-58 shooting.
She said she starting paying attention to stats, something she didn't do in high school, and got down on herself.
"It got in my subconscious and it was a lot of negative talk that I was hearing," she said. "I started questioning my ability as a player. All these people were telling me things I had to work on, and it was like every single thing you could possibly work on in basketball."
Tillis broke out of that with a 21-point effort in a home win against Maryland on Jan. 22, and has scored in double figures seven times since.
She said she benefited from the extra practice time in the week leading up to the tournament. It showed Saturday, when she had four assists and a steal in 28 minutes.
In addition, the Demon Deacons struggled inside against the bigger Blue Devils, who at times played the 6-foot-5 Tillis on the wing with the 6-3 tandem of Hunter and Bass inside.
Tillis went 2-for-3 from behind the arc, while Hunter and Bass combined for 14 rebounds, six steals and a blocked shot.
"They have so many weapons," Wake Forest coach Charlene Curtis said. "Their players are versatile. (Tillis) can play almost anywhere on the court, which makes her difficult to defend. And they now have I think a true inside game."
Duke had some trouble putting Wake Forest away. The Blue Devils led by 10 at halftime and pushed the lead to 15 early in the second half, but the Demon Deacons hung around by going 8-for-21 on 3-pointers in the first 25 minutes.
Wake Forest closed the gap to 53-44 on a three-point play from Brown with 12:53 left, but Tillis answered with six straight points to snatch the momentum back from the Demon Deacons.
She first hit a midrange jumper, then followed with a layup off a feed from Lindsey Harding and added two free throws for a 59-46 lead. Tillis later found Monique Currie for a layup and a 63-46 lead, one that would balloon to 25 points in the final 6_ minutes.