With their best defensive player, Jerel McNeal unable to play due to a thumb injury, the Golden Eagles struggled in running their offense and defense, only scoring 18 points in the first half, trailing 30-18 at halftime.
With McNeal's absence, the Spartans went inside with their big-men, outscoring Marquette by more than 20 points inside the paint.
Behind by a large amount, the Golden Eagles started shooting from three in hopes of getting closer.
Leading scorer Dominic James scored 18 points for Marquette while Wesley Matthews was the only other Golden Eagles player in double-figures with 10 points.
In a game where MSU coach Tom Izzo was facing his student, former Michigan State assistant and Marquette head coach Tom Crean, the Spartans jumped on the Golden Eagles early and often inside the paint.
Despite foul trouble, Drew Naymick and Marquise Gray played big roles in the win, maybe not on the scoreboard but on the boards.
The Spartans played one of their strongest defensive efforts of the season in shutting down the Golden Eagles to 49 points, who were nearly 24 points shy of their scoring average.
"It's been our mind-set the whole season to win with defense," Neitzel said. "We don't have the most dynamic weapons on the offensive end, so we've had to rely on our team defense the whole season - especially in this game."
Marquette missed their first eight shots of the game and Michigan States tight defense held the Golden Eagles scoreless for the first 9:40 of the game. The Golden Eagles didn't score until David Cubillan's 3-pointer from the left wing with 10:20 left in the first half.
"We had some new things, but bottom line, they executed their defense game plan really well, and we didn't," said Tom Crean.
Michigan State moves on to face #1-seed North Carolina in the second round of the NCAA tournament on Saturday night in Winston-Salem, North Carolina.