Illinois moved ahead of No. 15 Wisconsin and into a first-place tie with No. 5 Purdue in the Big Ten standings.
Tyson Walker scored a season-high 26 points and A.J. Hoggard had 15 for the Spartans, who never led and trailed by as many as 16 points in the second half.
Michigan State has lost four of five.
The Spartans cut the lead to two points several times in the final two minutes before Trent Frazier made a 3-pointer with 25 seconds left to put the game out of reach.