Caleb TerBush threw for 178 yards and two first-half touchdowns that stood up to Illinois' (6-2, 6-2 Big Ten) 14 unanswered points in the fourth quarter.
Rahem Mostert ran in the other TD for Purdue (4-3, 2-1) from 21 yards out to give the Boilermakers their second win in their last three games. Purdue has beaten Illinois in six of their last seven games.
Mostert's second-quarter touchdown was sandwiched between TerBush's 6-yard TD pass to Justin Siller in the first quarter and a 4-yard toss to Jared Crank with 7:48 to play in the first half.
Illinois, which generated 366 yards of total offense to Purdue's 304, battled back in the fourth quarter on a 16-yard TD run by Jared Ford with 8:12 to play and a 2-yard run by Nathan Scheelhaase with 54 seconds to go.
Scheelhaase finished the day 22-of-35 for 217 passing yards.