One of the biggest came after DePauw had retaken the lead midway through the third quarter.
Down 20-14, Conliffe and Chase Porter fumbled a bad handoff and DePauw's Grant Wright recovered at the Centre 5-yard line.
Three plays later, Spud Dick found Alex Koors in the right corner of the end zone for an 11-yard score that gave the Tigers a 27-14 lead with 7:15 to play.
Dick had plenty of time to throw most of the day and picked the Colonels apart, going 22-for-37 for 313 yards and three scores with one interception.
DePauw (2-0, 1-0 SCAC) outgained Centre 445 yards to 233 and held the ball for nearly 13 more minutes than the Colonels. Koors had eight catches for 220 yards.
Centre (1-2, 0-1) had just 32 yards rushing, led by Jonathan Pinque's 24 yards on seven carries.
"We just never got what we needed out of the big play," Frye said. "We didn't get anybody to make the big play."
Centre battles early in second half
But Centre made enough plays to take its first lead to open the second half.
Down 13-7, Conliffe hit Andrew Wells for 11 yards and Zack Hanson for 19 yards to get to the DePauw 40-yard line.
On a fourth-and-3, Conliffe found Pinque for a 5-yard gain to keep the drive alive, then hit Tyler Hinkle in stride three plays later for a 22-yard score to cap an 11-play, 62-yard drive and give Centre a 14-13 lead with 10:06 left in the third quarter.
Hinkel had five catches for 77 yards and a score.
"When we scored on that first drive coming back, that was really big for us. But they answered right back and that hurt us," Frye said. "We just weren't able to put it all together."
A personal foul call helped DePauw start its next drive at its 45, and Dick hit Alex Koors for a 39-yard touchdown on the third play to make it 20-14 just 62 seconds after Centre had scored.
Down 27-14, Centre drove to its own 45, but Chris Scarver picked off Conliffe's bomb to Hinkel to give DePauw the ball at its own 8 with 14:49 left and essentially seal the game.
DePauw got on the board to start the second quarter.
Starting from their own 20, the Tigers drove 80 yards in 10 plays, capped by Nick Etzcorn's leaping grab of Spud Dick's 2-yard fade pass into the right corner of the end zone 37 seconds into the second quarter.
The Colonels gave the ball right back to DePauw on their next series.
Ryan Woodard recovered a botched handoff between Conliffe and Pinque, giving the Tigers a first down at the Centre 31-yard line.
But Dick threw three straight incompletions, and Jordan Havercamp's 50-yard field goal was wide right.
After Centre was forced to punt again, Dick pump-faked and then hit Alex Koors for a 64-yard gain to the Colonels' 3. On the next play, Jon Ellis went in for a score and DePauw led 13-0 with 10:34 left in the half.
After five straight empty possessions, the Colonels finally got their offense going.
Conliffe hit Nate Hanson for a 17-yard gain and Hinkel for a 20-yard gain and Centre drove to the Tigers' 20-yard line. On the next play, Conliffe rolled left and lofted a pass to a wide open Chase Porter for a 20-yard score and Centre cut it to a 13-7 game with 8:15 left in the half.
Centre forced a punt and had the ball at the Tigers' 48, but Alex Fitch stripped Conliffe as he was going back to pass and recovered the fumble with 39 seconds left.
A 39-yard pass from Dick to Koors put the ball at the Centre 5, but Zack Sloan broke up a pass in the end zone, and Alex Ubelhart intercepted it to keep it a 13-7 game at the half.
"We took away a potential score, and that was big," Frye said.
DePauw - Nick Etzcorn 2 pass from Spud Dick (kick failed), 14:23.
DePauw - Jon Ellis 3 run (Jordan Havercamp kick), 10:34.
Centre - Chase Porter 20 pass from Grant Conliffe (John Starks kick), 8:15.
Centre - Tyler Hinkel 22 pass from Conliffe (Starks kick), 10:06.
DePauw - Alex Koors 39 pass from Dick (Havercamp kick), 9:04.
DePauw - Koors 11 pass from Dick (Havercamp kick), 7:15.
RUSHING-DePauw, Jon Ellis 24-123, Derrick Karazsia 11-25, Chris Collins 2-6, Spud Dick 5-minus 22. Centre, Jonathan Pinque 7-24, Chad Porter 4-8, Nate Hanson 1-6, Ned McCaster 2-5, Grant Conliffe 8-minus 11.
PASSING-DePauw, Dick 22-37-1-313. Centre, Conliffe 23-41-2-201.
RECEIVING-DePauw, Alex Koors 8-220, Brad Paus 3-18, Brayden Dahlstrom 2-17, Nick Etzcorn 2-13, Karazsia 2-10, Chris Gasbarra 1-15, Mark Branigan 1-12, Rocky Buchta 1-7, Dick 1-0, Mitch Willsey 1-0. Centre, Rob Pope 6-47, Tyler Hinkel 5-77, Pinque 4-15, Andre Wells 3-11, Hanson 2-28, McCaster 2-3, Porter 1-20.DEPAUW013140--27CENTRE0770--14
CBCFirst Downs2217Rushes42-13222-32Passing313201Total Yards445233Comp-Att-Int22-37-123-41-2Fumbles - Lost0-03-3Penalties11-8623-45