He defeated challenger Anthony Crolla in the fourth-round knockout at the Staples Center in Los Angeles, California.
Lomachenko's profile has grown exponentially in recent years as he headlined at Madison Square Garden, in Macau and other Los Angeles-area venues before his step up to Staples.
Referee Jack Reiss gave a standing eight count at the end of the third round as the Briton was being held up against the ropes amid a barrage of punches, but the fight continued. Crolla, not a big puncher with his 30% knockout ratio, had no answer for the onslaught and finally succumbed to a vicious right hook that Lomachenko masterfully looped around the high guard of Crolla.
"I want to fight Mikey Garcia, but we'll see".
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The 31-year-old Lomachenko delivered a devastating right hook to the temple that sent the Englishman crashing face first to the canvas just 58 seconds into the fourth round.
Lomachenko, a two-time Olympic champion, justified his overwhelming favourite status with a clinical 13th win of his professional career.
Lomachenko defended his WBA and WBO 135-pound belts with a violent fourth-round stoppage of Britain's Crolla on Friday night, demonstrating his pound-for-pound excellence with another virtuosic display. In the opening frame, Vasyl Lomachenko carefully gauges Anthony's movements with tricks and pressure. But he's devastated. He said: "I'm just so gutted for the team because of the work they did". "That's my goal. I want historic fights". The Mexican-American fighter has said in the past that he's felt slighted by Lomachenko's unwillingness to fight without the "proper conditions" in place.
The fight to make is one against Mikey Garcia, who suffered his first defeat last month in a welterweight title fight with Errol Spence Jr.