Sean Brady upset Leon Edwards with a dominant display as he submitted the Briton in the fourth round of the pair's welterweight bout at UFC London.
The American, 32, out-grappled Edwards throughout before ending the contest with a guillotine choke.
The defeat is 33-year-old Edwards' second in a row after losing his welterweight title to Belal Muhammad in July.
"I took this fight the day I got out of the hospital with my wife and our newborn baby. I knew I could do that and I think I belong in the top three for sure," said Brady.