The Spartans (26-8) started slowly but broke open an 8-8 game with a huge run that was worth a 17-point lead by halftime.
Michigan State advances to a third-round game Saturday in the Mideast Region against sixth-seeded Memphis (31-4), which defeated St. Mary's (Calif.) 54-52. St. Mary's won a first-round game Tuesday to get to the second round.
Nix had nine points in the first half, when the Spartans outscored Valparaiso (26-8) 24-4 over 10 minutes for a 32-12 lead. Michigan State opened the second half with a 14-4 run fueled with eight points from Nix.
The Spartans led by as many as 27 before Valparaiso cut it down to the final 11-point margin.
Nix's 23 points came on 10-of-17 shooting and he had nine offensive rebounds among his 15 for the game. Keith Appling added 15 points and Gary Harris 10 for Michigan State.
Ben Boggs paced Valparaiso with 15 points and Erik Buggs added 14.