Branden Dawson added 15 points and nine rebounds for the seventh-seeded Spartans, who advanced to the Sweet 16 for the seventh time in the last eight seasons under coach Tom Izzo. The Spartans will play the winner of the Oklahoma-Dayton game in Syracuse, New York on Friday.
With top seed Villanova having lost Saturday, it is the first time a No. 1 and 2 seed from the same region didn't advance to the Sweet 16 since Kentucky and Gonzaga in 2004.
The Spartans (25-11) stole a page from last year's regional semifinal win, limiting the Cavaliers to 29.8 per cent shooting. Virginia finished 2 of 17 from 3-point range.
Last year, the Spartans upset the top-seeded Cavaliers in the regional semifinal by holding Virginia to 35.1 per cent shooting.
The Cavaliers (30-4) were led by Anthony Gill's 11 points and Darion Atkins' 10 points and 14 rebounds.
The Spartans took a 23-18 halftime lead behind Trice's hot shooting.
The 6-foot, 175-pound senior guard made his first five shots, including three 3-pointers, and scored 13 of Michigan State's first 15 points in taking an 11-point lead.
The Cavaliers were cold from the onset.
They opened the game 2 of 10 from the field, but started to turn things around when Atkins rejected Alvin Ellis III's attempt at a one-handed dunk, leading to a corner 3-pointer from Ottawa's Marial Shayok at the other end.
But the Cavaliers could never get in a flow on offence, finishing the first half shooting just 26.7 per cent (8 of 30) from the field. Atkins kept the Cavaliers in the game with eight points and six rebounds in the first half.
Virginia cut the lead to two to start the second half behind two quick baskets by Justin Anderson. The Spartans countered with a 12-2 run led by Dawson, who had seven points during the stretch, including a three-point play off a fastbreak dunk.
Down six points, Atkins picked up his fourth foul with 8:36 left on what replays showed to be a clean block on Gavin Schilling and was forced to go to the bench.
Virginia got within five after Atkins returned to the lineup before Trice knocked down a clutch 28-footer with 1 second left on the shot clock to put the Spartans up 52-44 with 3 minutes to play.
Virginia finished with its second straight 30-win season, a school record.
But the Cavaliers fell earlier than expected in the NCAA Tournament despite spending most of the season ranked in the top five in the country.
Michigan State: The Spartans won despite shooting 20 of 33 from the free throw line. ... They led for more than 38 minutes of the game.
Virginia: Outrebounded Michigan State 39-32. ... Was 18 of 26 from the free throw line. ... London Perrantes and Anderson were a combined 4 of 17 from the field.
Michigan State: Will advance to the Sweet 16 to play the Oklahoma-Dayton winner.
Virginia: Season is over.