The Irishman had been out of action for 15 months but exploded into life from the first bell of the welterweight bout at UFC 246, charging at his opponent before bloodying his nose with several unorthodox shoulder strikes in the clinch.
McGregor then stepped back and a precision head kick high over the guard landed square on the jaw of Cerrone, who was also caught by a flying knee and crumpled to the mat as the Dubliner went for an early finish.
Cerrone was covered up as the rights and lefts rained down on him, prompting referee Herb Dean to call a halt to a brief one-sided contest within the first minute of the opening round.
"I made history here, I set another record: I'm the first fighter in UFC history to secure knockout victories at featherweight, at lightweight and now at welterweight, so I'm very, very proud of that," McGregor said in the octagon.
"Donald holds the record for most head-kick knockouts, I'm so happy to get him down with a head kick myself. I'm very, very happy, very proud.
"Who's going up and down divisions and stopping people like that?
"The UFC can strip fighters and gift other fighters make-believe belts in order to replicate my champ-champ status, but they can't give knockout victories across multiple weight divisions. Etch my name in history one more time."
The former two-weight UFC champion had been out of action since losing to bitter rival Khabib Nurmagomedov at the same venue in October 2018, while this was his first win inside the octagon in more than three years.
On that occasion, he stopped Eddie Alvarez to add the lightweight title to his featherweight crown, becoming the first fighter in the company to hold two belts simultaneously.
He went on to fame and fortune with a crossover boxing bout against American superstar Floyd Mayweather, but a couple of legal issues after his defeat to Nurmagomedov placed a doubt on whether he would return to the octagon.
McGregor, though, remains mixed martial arts' biggest draw, saying earlier this week he expects to pocket around 80million US dollars from his bout against Cerrone.
As for what is next, McGregor, who has been linked with showdowns against welterweight champion Kamaru Usman and 'BMF' titlist Jorge Masvidal, added: "Any one of these little mouthy fools can get it.
"It does not matter. I'm back and I'm ready. I like this weight division, I feel really good, it's good going up and down. God willing I came out of here unscathed.
"I'm in shape, I don't believe I'm there yet, I've still got work to do to get back to where I was, so I'm going to party tonight and celebrate, spend time with my family and get back in the gym and train."
While McGregor was the betting favourite in the Vegas headliner, he was relatively untested at 170lbs and came in against an opponent with the most wins (23) and finishes (16) in UFC history.
But Cerrone proved no match for McGregor, who consoled the 51-fight veteran afterwards in an act that underlined the respect between the pair.
Cerrone said of McGregor's shoulder blows: "I'd never seen anything like that, they threw me way off guard. He busted my nose then stepped back and head kicked me. I was like 'oh man, it's happening this fast? I got my ass whipped early'."