Centre has not won or shared a league title since 1995, when it was an SCAC tri-champion.
"We're in the driver's seat, but we've got to take care of business," Frye said.
Centre drove the ball down DePauw's throat Saturday, rushing for 220 yards and possessing the ball for nearly 37 minutes.
DePauw (5-3, 3-2) entered the game with an offense that ranked second in the conference only to Trinity, but the Colonels found a way to keep the Tigers from running wild.
"One way you can keep them from scoring is don't let them have the ball," Frye said.
Lorenzo Engleman powered the Centre offense with 186 yards rushing and 61 yards receiving, and Frye said a tremendous effort by the line kept that offense on the field and DePauw's on the sideline.
"The offensive line did an outstanding job of controlling the football," Frye said.
Centre had 41 rushing attempts, including 31 by Engleman, who ran for a 31-yard score in the second quarter and had 120 yards rushing at halftime.
"Lorenzo had another outstanding game," Frye said.
Quarterback Brian Beh-rendt, back on the field a week after suffering a shoulder separation, turned in a gritty performance, going 28-for-42 for 279 yards with two touchdowns and no interceptions.
"He just gutted it out," Frye said. "He was probably playing at 70 percent, but he just played a great game."
The winning score was Blandford's second touchdown run of the day, and it came on a play that was only intended to set up a field goal.
John Wallace missed a 26-yard field-goal attempt on DePauw's overtime possession, so Centre was in control when it got the ball at the 25-yard line. After a first down, the Centre coaches decided to try a field goal on third down.
The handoff to Blandford was designed to move the ball to the left hash mark, where kicker Chris Thompson wanted it. But when the DePauw defense fell for a fake to Engleman, Blandford was in the clear and on his way to the end zone.
Centre led 21-7 at halftime, then saw DePauw tie the game early in the fourth quarter.
The Colonels regained a 28-21 lead with 5:34 to play on Behrendt's 3-yard touchdown pass to Rhese McKenzie, but DePauw scored 52 seconds later on a 68-yard pass from Ross Wiethoff to Brian Culp.
Nate Woodall had seven receptions for 96 yards for Centre, and David Crowley had five catches for 95 yards.
The Colonels finished with 499 yards, while DePauw had 430.
John Ortega had a game-high 14 tackles to lead the Centre defense, including 10 solos. Nathan Fell followed with eight tackles, and Kevin Tytus had six. Jacob Coleman intercepted a pass.
Centre has an open date before its season finale against Rose-Hulman, and Frye said it comes at a good time for the banged-up Colonels.
"Right now it is a good time," he said.