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.
"I thought it will be very hard for me, because his style is always in defense", said Lomachenko, still smiling despite a cut near his left eye from a fourth-round head butt. Lomachenko's next fight is likely to be even bigger, whether as a unification bout or a showdown with one of the other lightweight greats of this era.
Campbell could be a potential opponent for Lomachenko as he has earned a mandatory shot at the WBC title now held by Mikey Garcia, who is yet to announce if he will vacate the belt.
Lomachenko headlined at Staples Center for the first time in his brief professional career.
The knockout punch was so loud it could be heard by those sitting outside the ring. Commey's injured hand forced Lomachenko's promoters to make this fight with Crolla, rather than surrender his WBA belt.
Crolla dropped to 34-7-3 as he landed just a handful of punches and only survived the third round because of the bell. Lomachenko wanted to fight IBF champion Richard Commey, but Commey suffered a hand injury.
It's worth mentioning that Vasyl's Staples Center fight card served as the official launch for an ESPN+ boxing program curated by Top Rank promotions, whose chairman Bob Arum was eager to sing the Ukrainian's praises after the bout. He has won the last three of his fights against Ricky Burns, Edson Ramirez, and David Yordan which has put him back into world title contention. Crolla lost the title to Jorge Linares back in 2016 and lost the rematch as well. The knockout win allowed Lomachenko to retain his WBO and WBA lightweight titles.