It was the most lopsided NCAA Tournament loss for a defending champ in nearly three decades.
Carsen Edwards scored a career-high 42 points, and Purdue knocked defending champ Villanova out of the tournament with an 87-61 rout.
The last time a defending champ was beaten that badly was when Loyola-Marymount ran past Michigan 149-115 in 1990.
Matt Haarms added 18 points and nine rebounds for the Boilermakers (25-9), who advanced to their third straight Sweet 16.
Eric Paschall had 19 for Villanova (26-10), which saw its quest for a third national title in the last four seasons fall short. Fellow senior Phil Booth scored 15 points, putting him over 1,500 for his career.
Edwards has battled a sore back and had been in a recent shooting slump, making just 7 of 23 shots from the field in Purdue's first-round win over Old Dominion.
He found the bottom of the net early and often against Villanova, making 12 of his 21 shots, including nine of 16 from behind the arc.
Some other recent tournament blowouts suffered by defending champs:
1998: Utah beat Arizona 76-51.
2001: Arizona beat Michigan State 80-61.
2011: Arizona beat Duke 93-77.
2018: Texas A&M beat North Carolina 86-65.