Western Illinois scored 10 points in the opening 80 seconds of the fourth quarter to close within 20-18 but Blakemore went 51 yards to score with seven minutes remaining and added a 6-yard TD with 1:17 to go.
The Redbirds stifled the Leathernecks on the ground, holding them to minus-5 yards on 29 attempts. Illinois State outgained Western Illinois 461-194.
The Redbirds (2-0, 1-0) led 13-9 at halftime and extended their lead to 11 points on Cole Muller's 6-yard run in the third quarter.
Zak Annexstad was 18 of 29 for 185 yards passing and a touchdown to Cam Grandy.
Matt Morrissey was 22 of 40 for 199 yards passing with a touchdown in the air and on the ground for the Leathernecks (0-2, 0-1).