Cody Zeller poured in 18 points on 7-of-12 55, on Tuesday at Assembly Hall.
Victor Olapido netted 13 points, Verdell Jones III finished with 12 and Christian Watford had a double-double with 10 points and 14 rebounds for the Hoosiers (23-7, 10-7 Big Ten), who have won three straight games to get on a roll heading into the Big Ten Tournament, which begins on March 8. Jordan Hulls rounded out the double-figure scorers with 10.
Indiana improved to 17-1 at home and has beaten a top-5 team at Assembly Hall for the third time this season. They took down top-ranked Kentucky on December 10 and Ohio State on December 31.
Michigan State was carried by Draymond Green, who finished with 29 points on 10-of-17 from the floor to go with eight rebounds. Green's 10 field goals matched the offensive output of all of his teammates combined.
The Spartans (24-6, 13-4) blew a chance to wrap up the Big Ten regular season title and had its seven-game winning streak snapped.