Appleby was 15 of 20 for 202 yards. He ran for another 76 yards on seven carries.
Akeem Hunt carried the ball 30 times for 177 yards and a touchdown.
The Boilermakers (3-3, 1-1 Big Ten) took a 24-14 lead on an 80-yard touchdown pass from Appleby to Danny Anthrop in the third quarter.
Big plays sank the Illini (3-3, 0-2). Besides the 80-yard touchdown, Purdue had plays of 62, 54 and 53 yards.
Wes Lunt led Illinois with 332 yards and three touchdowns. But he limped off the field with help early in the fourth quarter after a big hit and did not return.