Ngannou (13-3) dropped Velasquez with a short right uppercut just moments into Sunday's UFC Fight Night main event. The heavyweight bout headlined the UFC's first live event on ESPN, from Talking Stick Arena.
Widely regarded as one of the best heavyweights of all time, Velasquez (14-3) never had a chance to show what he has left in the tank at age 36. Ngannou, who fights out of Cameroon and France, finished him off with a single flurry. It was the ninth first-round stoppage of Ngannou's career.
"I stood a little too close too early," Velasquez said. "That's when he's dangerous. That's how it happened. What are you going to do?"
Ngannou is fully back on track after a difficult first half of 2018. He was dominated in a challenge of then-heavyweight champ Stipe Miocic in January 2018, then lost a decision to Derrick Lewis last summer in a bout in which he looked tentative and lost. But Ngannou ended the year with an explosive first-minute knockout of Curtis Blaydes in November, and on Sunday night he repeated the trick against a former champion.
Ngannou wants a title shot after KO win.
Francis Ngannou tells Pedro Gomez he wanted to fight Cain Velasquez two years ago and he's looking to fight for the gold once again.
"I promised you guys: I'm back," Ngannou said. "You're going to see me around again. I told you yesterday I have some surprise for you. I hope you like it."
Velasquez had not fought since he rebounded from losing his title with a knockout of Travis Browne in July 2016. Since then, he has had to deal with bone spurs in his back, the latest in a litany of injuries the 36-year-old has faced. But his inactivity also was by choice, as he became a father for the second time last year and wanted to devote himself to his family during his wife's pregnancy and his son's first year.
"Man, I thought I was super ready for this fight, even coming in here, super calm and relaxed, ready to go," Velasquez said. "This is why this sport is so great: You never know what's going to happen."