Peter Jok had 19 points for the Hawkeyes (10-3, 1-0 Big Ten), who toppled a No. 1 team for the first time in 16 years.
Iowa never trailed in what turned out to be a surprisingly easy win over the Spartans (13-1, 0-1).
The Hawkeyes led by as many as 19 points in snapping a nine-game losing streak against Michigan State.
"It was one of the rare times in my career I thought we got, for (lack) of a better choice of words, punked," Michigan State coach Tom Izzo said. "We got outhustled."
Eron Harris scored 21 points to lead the Spartans, who were playing their second game without Valentine, their leader in scoring, rebounds and assists. It also was their first game since Izzo's father, Carl, died Monday.
Izzo refused to use Valentine's absence as an excuse, pointing instead to what he called a "disappointing effort."
"Zero," Izzo said about how much Valentine's not playing hurt the Spartans. "That had something to do with not making baskets. But it had nothing to do with the effort you give."
Valentine is likely to be out through next week after arthroscopic surgery on his left knee.
The Spartans looked so underwhelming in beating Oakland 99-93 last week without him that the Hawkeyes, who are unranked, were actually a slight favorite.
From the opening tip, it was easy to see why.
Iowa kept Michigan State off the scoreboard for nearly 6 minutes, and despite having star Jarrod Uthoff on the bench with foul trouble, the Hawkeyes went up 31-17 on Dom Uhl's banked 3 with just more than 5 minutes left in the first half.
The Spartans trailed by double digits at halftime for the second straight game, this time 37-23.
But the Hawkeyes aren't Oakland, and the Spartans simply couldn't keep up.
Consecutive 3s from Jok made it 58-39 with 11 minutes left, and Iowa cruised to its first win over a No. 1 team since beating Connecticut in former coach Steve Alford's debut in 1999.
"We really sustained effort and paid attention to the details," Iowa coach Fran McCaffery said. "I think we disrupted their offense quite a bit."
Matt Costello had 17 points for Michigan State.
"We struggled a lot defensively," Costello said. "They just got bucket after bucket, and we couldn't stop them."
Michigan State: Valentine entered Big Ten play averaging 18.5 points, 8.3 rebounds, 7.1 assists per game. ...The Spartans play four of their first six Big Ten games on the road but close league play with four out of six in East Lansing. ... Alvin Ellis III inadvertently deflected an inbounds pass into Iowa's basket early in the second half.
Iowa: The Hawkeyes lost to Dayton, Notre Dame and Iowa State in nonconference play by a combined 12 points. ... Iowa held a moment of silence for Izzo's father, and its fans followed with an ovation. ... Iowa was the second team from its state to take down the top-ranked team at home this season. Northern Iowa knocked off North Carolina in November in Cedar Falls.
QUOTE OF THE NIGHT
"My dad was kind of a two-job, blue-collar immigrant that worked his posterior off most of his life, and that's what I asked of my team: 'Don't honor him with a win. Honor him by how we play,'" Izzo said. "That's been the most disappointing of all the things that've happened in the last two days."
Iowa redshirt freshman Nicholas Baer missed a tough layup late in the first half, and although he was clearly gassed, he got back in time to block Matt McQuaid's 3-point try. It was yet another moment of unexpected brilliance from the redshirt freshman, who still isn't even on scholarship. McCaffery said earlier this month that Baer, who had 11 points, will get a full ride as soon one becomes available.
Michigan State plays at Minnesota on Saturday.
Iowa visits No. 14 Purdue on Saturday.
Mike Krzyzewski says he has good reason to be excited for next season thanks to a combination of Duke's incoming freshmen and a core of experienced upperclassmen.
Georgia guard Juwan Parker has been awarded a medical redshirt, leaving him with two years of eligibility, after missing the 2015-16 season with a partially torn Achilles tendon.
Forward Trevon Bluiett has withdrawn from consideration from the NBA draft and will return to Xavier for his junior season.