The Spartans went on a 26-5 run in the first half to take control, and cruised to an easy victory.
Michigan State (26-8) will play the winner of the Memphis-St. Mary's game on Saturday when coach Tom Izzo's Spartans will be shooting for a spot in the round of 16 for the fifth time in six years.
The Crusaders (26-8) were no match for Michigan State in their first NCAA tourney in nine years, just as they weren't as a first-round loser in 2000 to the eventual champion Spartans.
Valpo had enough size to match up, but didn't have enough strength.
The Crusaders didn't seem worried about the 6-foot-9, 270-pound Nix when asked about him the day before the game.
Valpo's 6-8, 240-pound forward Kevin Van Wijk nonchalantly said he and his teammates faced similar players in the Horizon League. If that's true, it didn't seem to prepare Van Wijk and his fellow post players for Nix's brute force, relatively nimble feet and soft hands.
Nix had nine points in the first half when he made his fourth shot to put Michigan State ahead 32-12. At that point, he had as many field goals as the Crusaders' entire team. That basket was scored after backing down Bobby Capobianco so much that the 6-10, 245-pound forward fell on his back as if he was hit by a linebacker. Nix scored 14 in the second half, falling two points shy of matching his career high.
Van Wijk, meanwhile, missed both of his shots in the first half. He fouled out without making any of his six attempts and finishing with two points — well below his 12.7-point average. Valpo's other post player and leading scorer, Ryan Broekhoff, scored eight points — half his average — on 2 of 11 shooting.
Erik Buggs scored 14 and Matt Kenney had 10 points for the Crusaders, whose coach Bryce Drew called as many timeouts as he could to slow down the Spartans.
It didn't work.
While Nix dominated on the inside, Michigan State guards Keith Appling and Gary Harris gave the team offensive balance by making jumpers. Appling scored 15 points — making three 3-pointers — and Harris had 10 points.
When Valpo went to a zone early in the game when the score was tied at 8, Harris made a 3-pointer to put the Spartans ahead for good. He made another 3-pointer during the game's decisive run, making his extra work earlier in the week pay off for him and his team.
More than an hour after Monday's practice, Harris was back in the gym. He got a collapsed ball-return machine out of a corner by himself, wheeled it under a rim and set it up to put up some high-arcing shots. He made 52 of his first 71 shots, mostly from long range, during a personal workout thanks to a sweet stroke that has served the freshman — and the Spartans — well this season.