Illinois defeated Purdue 43-27 in Week 6, with the Illini exploding for 27 points in the second quarter to seize control of the game. Luke Altmyer led Illinois' offense, completing 390 passing yards and connecting with Hank Beatty twice for touchdowns, including a 62-yard score in the second quarter that exemplified the visitors' aerial attack. Ca'Lil Valentine rushed for 95 yards to support the passing game.

Purdue struck first with a 7-0 first-quarter lead, but Illinois' second-quarter surge proved decisive. The Illini added 13 more points in the third quarter, extending their advantage before a quiet fourth quarter saw Illinois add just 3 points while Purdue managed 6. Illinois' defense made critical plays throughout, including a crucial stop in the second quarter. Despite Purdue's Michael Jackson III recording 94 receiving yards, the home team couldn't overcome Illinois' offensive firepower. Illinois' 16-point victory exceeded the 7-point spread and pushed the game over the 54.5-point over-under.