Thomas Brown returned a fumble 59 yards for a touchdown for Wake Forest and Tanner Price was 12 of 27 for 124 yards in his final home game with a 6-yard touchdown to Spencer Bishop and an 11-yard touchdown run.
But the interception he threw to Ross Cockrell with 2:30 left was the Demon Deacons' second turnover of the fourth quarter. That clinched their fifth straight losing season and kept them out of the bowl picture for the fourth time in five years.
"That's a hard one to take," Price said.
Crowder finished with 121 yards receiving on 10 catches for Duke, which was playing as a ranked team for the first time since the 1995 Hall of Fame Bowl.
They beat Wake Forest for the second straight year -- after losing 12 straight in the series -- and reached the nine-win mark for the first time since 1941.
"We want to keep winning," Crowder said. "That's pretty much our main goal right now."
Price capped Wake Forest's opening drive of the second half with an 11-yard touchdown run that put the Demon Deacons up 21-14, before Boone tied it three plays later with his deep TD pass to Crowder.
Boone's 20-yard scramble to the Wake Forest 3 on Duke's next series set up Connette's touchdown run that gave Duke the lead with 3:21 left in the third.
Wake Forest had one last chance after Ross Martin missed a 48-yard field goal with 4:11 left. But Cockrell intercepted Price's late pass over the middle and the Blue Devils ran out the clock to seal their first seven-game winning streak since 1994.
Price said the intended receiver, Sherman Ragland III, stopped his post route -- "I think maybe he thought I was scrambling," Price said -- and Cockrell jumped in and picked off the pass.
That came after Duke's defense, which has allowed just three offensive touchdowns in the fourth quarter this season, forced Josh Harris to fumble and defensive end Kenny Anunike sacked Price on consecutive plays to push the Demon Deacons out of field goal range.
"That's kind of been our thing all year," Cockrell said. "Our motto is just to finish. ... We know when the game gets tough, it's in the fourth quarter. That's when you've got to be at your best."
For a while, though, it looked like Duke's first appearance in the Top 25 in nearly two decades was going to be a short one because its offense couldn't get going until midway through the second quarter.
Once it did, it was tough to stop: Duke scored on four of five possessions, and was stopped only when it took a knee to end the half.
Boone's shorter TD pass to Crowder got Duke's offense started, and his back-shoulder fade to McCaffrey tied it at 14 with 1:11 before the break.
The Demon Deacons' offense hadn't scored a touchdown since the second half of the Miami loss on Oct. 26 -- and on Duke's second possession, their defense started the scoring.
Brown turned receiver Isaac Blakeney's fumble into a scoop-and-score with 5:02 left in the first. Wake Forest then followed that with its first offensive TD of the month when Price's pass to Bishop made it 14-0 three plays into the second.
"We know that once we kind of get things going, that offense is pretty tough to defend," Crowder said. "As long as we kept it in that little range of 14, once our offense started, we'd make it a ball game."