Andrew Maxwell threw for a career-high 290 yards and two touchdowns as visiting Michigan State scored the game's final 17 points to deny Indiana's upset bid.
Le'Veon Bell scored on a pair of short touchdown runs and the Spartans' defense bottled up the Hoosiers in the second half after Indiana ran out to a 17-0 first-quarter lead and racked up 280 yards of total offense in the opening half.
Maxwell connected on 24 of 40 passes, including a 36-yard scoring strike to Bennie Fowler with 6:35 to play that put Michigan State (4-2, 1-1 Big Ten) ahead for good and gave the team its fourth consecutive win in the series.
Bell rushed for 121 yards on 37 carries and true freshman Aaron Burbridge, making his first start, had eight catches for 134 yards for the Spartans, who limited Indiana to 37 yards of offense and one first down in the second half.
Cameron Coffman threw for 282 yards - 256 in the first half - and had first-quarter TD passes to Stephen Houston and Ted Bolser as the Hoosiers (2-3, 0-2) bolted to a 17-point lead. He also connected with Shane Wynn on a 17-yard scoring strike in the second quarter as Indiana took a 27-14 lead into halftime.
GAME NOTEBOOK: Spartans TE Dion Sims, who entered the game as the team's leading receiver, was injured in the first half and returned to the sidelines with crutches and a walking boot. ... The Hoosiers held a halftime lead in a conference game for the first time since Oct. 29, 2009 against Northwestern, but punted on their first six second-half possessions. ... Burbridge became the first freshman for Michigan State to post a 100-yard receiving game since Terry Love in 2004.