Cormier (22-1) became the first fighter in UFC history to officially hold two titles simultaneously and successfully defend both. He submitted Lewis (21-6) via rear-naked choke at 2 minutes, 14 seconds of the second round in a bout that headlined UFC 230 at Madison Square Garden.
It was the first UFC heavyweight title fight at New York's historic venue, and Cormier delivered another iconic image for the photo archives. All three UFC cards held in Madison Square Garden have featured victories by two-weight champions, in Cormier, Georges St-Pierre and Conor McGregor.
"It's history, baby," said Cormier, who improved his heavyweight record to 15-0 (4-0 in UFC). "History in the making -- Daniel Cormier, one of the best of all time!
"I think a lot of people have to understand, I've been doing this for nine years. I've fought at the championship level for eight of them. There are no surprises with me. If you have a puncher's chance, that's not enough. You have to be one of the best in the world to even compete."
Saturday's fight marked Cormier's first heavyweight title defense, and the victory kept a planned matchup against WWE star Brock Lesnar intact for early 2019.
"Brock Lesnar, when you come, bring that new WWE title," Cormier said. "I feel like being a WWE champion, too. Let's go, Brock. Bring that belt with you if you come to my house."
Cormier was a significant betting favorite going into Saturday, and it was clear why. The former U.S. Olympic wrestler easily took Lewis down and, although Lewis managed to work back to his feet on several occasions, Cormier stuck to him and gave him no space to land any offense.
Lewis threw several haymakers in the second round with bad intentions, but Cormier slipped the shots and calmly went about taking him back to the floor. The finish came after Lewis tried to turtle up and stand. Cormier transitioned to his back and sank in the choke.
Cormier finished the fight 4-for-4 on takedowns and outlanded Lewis 19-4 on significant strikes, according to FightMetric.
Cormier, of Louisiana, has said he will retire by his 40th birthday in March. The American Kickboxing Academy product has only lost to former light heavyweight champion Jon Jones. Jones will fight Alexander Gustafsson for the light heavyweight championship Dec. 29, at which point Cormier will give up his 205-pound title.
Both Cormier and Jones have said they don't feel a third fight between them is necessary. Cormier lost to Jones twice at 205 pounds, but the second fight in July 2017 was changed to a no-contest after Jones failed a drug test. White told ESPN in the past week, however, that he feels a third fight between them is inevitable.
Lewis, of Houston, earned the title shot with a 9-1 record in his past 10 bouts. He was coming off a quick turnaround, having just fought Alexander Volkov at UFC 229 on Oct. 6.
"You know what surprised me?" Cormier said. "When I took that last shot, he punched me in the eye on the way in. I was blinking for about 30 seconds, thinking, 'What in the world was that?' Everything he did held unbelievable power. What a guy Derrick Lewis is."