Vic Darchinyan was beaten for the first time in his career on Saturday to lose his grip on his IBF flyweight title.
Darchinyan was knocked down after 38 seconds of round five
The Armenian-born Australian, making his seventh defence, was knocked out in round five by Philippino Nonito Donaire, who dominated from the start.
Donaire tagged Darchinyan with a left hook, leaving the southpaw, 31, on the canvas for several minutes.
On the same bill in Connecticut, Travis Simms lost his WBA light middleweight title to Haiti's Joachim Alcine.
Both fighters had points deducted for excessive clinching, but American Simms, making his third defence, was knocked down in the ninth on his way to a comprehensive points defeat.
Darchinyan said he wanted the chance to avenge his loss to Donaire.
I shut him up and he still wouldn't admit in the ring after the fight that I beat him
"I'm very disappointed," he said. "He caught me with a very good shot. I'll be back. I definitely want a rematch."
Donaire's win was doubly satisfying, given Darchinyan had beaten elder brother Glenn in 2006.
"I came in here as an underdog," said Donaire, 24.
"Nobody believed in me, but I did it. I think the key for me was every time Darchinyan threw and landed, I punched back and that got him thinking. It took the bully out of him.
"I shut him up and he still wouldn't admit in the ring after the fight that I beat him."
"This fight wasn't just for me, it was for my family and the Filipino people, too. I could feel their energy tonight. I felt so good in the ring."