After slipping on a couple of attempted strikes, Holloway jumped to action and let punches fly before McGregor worked his way back to his feet.
But after McGregor fell to the canvas again when he attempted a punch, Holloway was loath to strike his fallen opponent and instead gestured to referee Mike Beltran that McGregor might be hurt.
When McGregor got back to his feet again, an attempt to put weight on the leg saw him wince and clutch at it, which forced Beltran to call it off.
It was a deflating way for the card to end, with serious questions now hanging over McGregor’s future in the sport.
Speaking to media after the event, UFC boss Dana White said it was suspected McGregor had torn the ACL in his right leg.
“Everybody who knows anything about the fight business, and it’s been a big topic of discussion leading up to this fight, five years off in this business is rough,” White said.
“I was expecting at least a one-round war. Who knew what Conor was capable of as far as cardio and whatever else after a five-year layoff?
“There you go. We’re assuming it’s a blown ACL.”
With the result, Holloway became the fourth UFC fighter to claim wins by knockout in three different divisions, alongside McGregor, American Jared Cannonier, and the first New Zealand-born UFC champion Robert Whittaker.
Whittaker achieved the feat earlier in the event, suggesting the light heavyweight division perhaps should fear The Reaper.
In his first appearance at 92.9kg, Australian Whittaker made his presence felt.
The 35-year-old claimed a third-round TKO win over No 12-ranked Nikita Krylov, landing a strong right hand in the final round that saw Krylov concede defeat immediately.
It was a big moment for Whittaker, who had run his race at middleweight (83.9kg) – a division in which he was champion between July 2017 and October 2019.
Jumping straight into the deep end in his light heavyweight debut, Whittaker got the test he expected from Krylov.
The size difference was clear and Krylov tried to use that in the first round as he worked Whittaker to the fence and looked to implement his grappling.
Australian-based Whittaker found himself in a few uncomfortable positions in the round, but managed to thwart Krylov’s efforts and end the round on his feet, throwing punches.
It was a tight first round, but Whittaker began to take over in the second. While he was almost exclusively head-hunting with his strikes, Whittaker was having plenty of success with his punches and, as the faster, more explosive fighter, his movement was causing Krylov concern.
Whittaker appeared to have Krylov in trouble in the second half of the round, before continuing in the same fashion when the third round began.
It was a right hand to the jaw that ended the fight, with Whittaker catching Krylov as he tried to move back out of striking distance.
The strike didn’t noticeably wobble Krylov, but he immediately moved his jaw a couple of times before giving Whittaker a thumbs up and having the referee step in to end the bout.
White said in the post-event press conference that Krylov was transported to hospital for assessment, but did not break his jaw as many people thought he might have done.
Christopher Reive joined the Herald sports team in 2017, bringing the same versatility to his coverage as he does to his sports viewing habits.