DURHAM, N.C. -- DePaul kept taking the ball from Duke with its intense press, and answering seemingly every big Blue Devils bucket with a 3-pointer.
That energy and efficiency sent the Blue Demons into the second weekend of the NCAA women's tournament.
DePaul upset Duke 74-65 on Monday night in the second round after hitting a season-high 14 3-pointers.
Seven of them came immediately after baskets by the Blue Devils.
"We have the greenish green light," guard Brittany Hrynko said. "[Coach] doesn't mind us taking 3s. He said as long as we take them, we have to defend and rebound."
Megan Rogowski scored 22 points with six 3s, Megan Podkowa added 18 points and Hrynko had 14 for the seventh-seeded Blue Demons (29-6).
"It has to absolutely be the biggest win for this group of young women this season," coach Doug Bruno said of a team that has won 18 of 19.
They earned their third appearance in the round of 16 by hitting those 3s and forcing second-seeded but injury-depleted Duke into 21 turnovers with their high-pressure defense.
DePaul will play the James Madison-Texas A&M winner on Saturday in the Lincoln Regional semifinals.
Elizabeth Williams scored 12 points and blocked seven shots. Seniors Haley Peters and Tricia Liston each added 11 in their final game at Cameron Indoor Stadium.
Duke (28-7) led for only 12 seconds and became the first top-four seed to lose in the tournament.
The Blue Devils -- who made four straight appearances in the regional finals -- became the first No. 2 seed to lose this early since Xavier lost to Louisville in 2011.
"They were on top of our ball handlers, and we didn't handle it very well," Peters said. "We just got a little bit rattled, I think, by how aggressive and how much pressure they put on us."
Jasmine Penny added 11 points for DePaul. The Big East champs were coming off a 104-100 win over Oklahoma in the first round, the highest-scoring regulation game in tournament history.
They joined Connecticut, Notre Dame and North Carolina as teams to come into Cameron this year and beat the Blue Devils.
They won this one with defense, using relentless pressure to suffocate a Blue Devils team with no healthy point guards after season-ending knee injuries to senior Chelsea Gray and sophomore Alexis Jones.
"It takes a lot of energy and effort for those players to commit themselves to defend over 94 feet," Bruno said. "They had the strength inside, and we had the strength with our quickness, and that's what a pressure package is all about."
Ka'lia Johnson scored 11 points and Oderah Chidom added 10 for Duke, which lost an NCAA tournament game at Cameron for the first time since 1996 and was denied its 17th regional semifinal berth in 18 years.
Duke had one last chance to make things interesting after Liston hit a layup after a steal to make it 67-60 with 1:45 left and Hrynko missed the front end of a one-and-one.
But Penny blocked Liston's layup, and after the teams traded turnovers, DePaul bled the clock before Duke fouled Jessica January with 1:09 left and she hit a free throw.
Liston's 3 went in and out, and Rogowski hit two free throws with 42.1 seconds left to push the lead back to 10.
Duke had closed to 49-46 on Chidom's layup with 7 minutes left.
Penny countered with a jumper in the lane and Hrynko followed with a 3 in front of the DePaul bench -- and afterward held her shooting hand high for a moment.
"I'm not sure that [Hrynko] is going to hit those shots again," Duke coach Joanne P. McCallie said. "It was hard to extend and attack on her because she was so far out on those 3s."
Rogowski hit one to push the lead to 57-48, and she then gave DePaul a double-figure lead on its next possession with two free throws with 5:02 left.
By then, Duke was on its way to dropping to 21-2 in NCAA tournament games at Cameron.