The perennial UFC lightweight contender shocked McGregor, beating him via TKO after swarming him with punches at 2:32 of the second round Saturday night in the main event of UFC 257 in Abu Dhabi, United Arab Emirates.
Poirier first hurt McGregor on the right leg with kicks to the calf. With McGregor's leg compromised, Poirier ripped off a series of hard-punching combinations. The closing blow was a shovel right hand that dropped McGregor. Poirier followed on the ground, and referee Herb Dean stepped in to call it, marking the first KO or TKO loss of McGregor's 13-year career.
McGregor and Poirier had fought before, with McGregor winning a featherweight match by first-round TKO at UFC 178 in 2014.
"I felt his presence less, his aura less," said Poirier, who entered the fight as a plus-275 underdog. "I just saw another fighter tonight. I think the first time, I was kind of a deer in the headlights, you could say. This time, I was just fighting another man -- another man who bleeds just like me. And I knew that."
Current lightweight champion Khabib Nurmagomedov has made it clear he intends to retire, but whether or not he relinquishes the belt, Poirier has now put himself in the driver's seat for a title shot.
"I feel like I've done it all except I can't walk away and say I'm the champ," Poirier said. "I want to be the champ. When you're the champ, you can say you're the champ forever."
ESPN had Poirier ranked No. 3 and McGregor No. 10 in the world at 155 pounds.
McGregor had a strong first round. He landed several hard left hands and a nice shovel right hook that snapped Poirier's head back. Poirier took McGregor down, but McGregor got back up with relative ease.
The two fought in the clinch, with McGregor landing some hard shoulder strikes, like the ones he hurt Donald Cerrone with a year ago. Poirier lost the round, but he did land hard kicks to the calf, which came into play later.
In the second round, McGregor landed hard combos but was having a hard time checking Poirier's calf kick. McGregor started catching Poirier's kicks and landing punches. But the damage was being done nonetheless.
In the finishing sequence, Poirier landed a hard kick to McGregor's right calf that clearly hurt him. Poirier got McGregor against the cage and let loose with a hard combination that rocked McGregor -- and then another, culminating with a beautiful right hand that dropped McGregor.
"The game plan was to kick, wrestle and box," Poirier said. "[Coach] Mike Brown was big on me throwing calf kicks in this fight, and it worked."
McGregor admitted being hurt by the calf kicks, saying he was "badly compromised" by them.
"It's hard to take. The highest highs and the lowest lows in this game," McGregor said at his postfight news conference. "My leg is completely dead. Even though I felt like I was checking them, it was just sinking into the muscle at the front of the leg and it was badly compromised."
"I didn't adjust and that's it," McGregor added. "Fair play by Dustin. I'm very happy for him."
UFC president Dana White said at his postfight news conference he thinks Poirier will fight Michael Chandler for the lightweight title next, adding that a recent conversation with Nurmagomedov about his UFC future "didn't sound too positive."
"He said to me, 'Dana, be honest with yourself. I'm so many levels above these guys, I beat these guys,'" White said of his talk with Nurmagomedov. "I don't know. But it doesn't sound very positive. We'll see."
"I'm gonna talk to Khabib and see if he wants to defend that title," White added. "And if he doesn't, I won't push it anymore."
Poirier said he would be interested in a rematch with McGregor but that he doesn't want his next fight to be against Chandler, because Chandler just made his UFC debut on Saturday. Chandler knocked out Dan Hooker in the first round.
"I can guarantee I'm not fighting Michael Chandler," Poirier said. "They can do whatever they want with the division.
"It's not a knock against him. It's just my feeling toward the division and the sport."
Poirier outlanded McGregor 48-29 in significant strikes, with 18 of those being leg strikes, per UFC Stats.
It was McGregor's first fight since a 40-second knockout of Cerrone at UFC 246 in January 2020 and his first time at lightweight since a 2018 loss to Nurmagomedov. McGregor has fought in the UFC just three times since 2016 but has vowed to stay active this year, saying this week he wanted to fight seven times in the next 18 months.
Asked what's next for him, McGregor said he thinks there are several good matchups out there. He said he hopes for a third fight with Poirier.
"I'll adopt a different approach for the trilogy with Dustin," McGregor said. "Those leg kicks are not to be messed with. The calf kick, the low calf kick, I hadn't experienced that."
White said he thinks Saturday's defeat will make McGregor "hungrier."
"There's two ways this goes: hungrier or 'I'm done,'" White said.
UFC 257 took place in front of a limited amount of fans at Etihad Arena with COVID-19 protocols in place. It was the first UFC pay-per-view event with ticketed fans since last March because of the coronavirus pandemic.
Poirier (27-6, 1 NC), the former UFC interim lightweight champion, has just one loss in his past nine fights -- to Nurmagomedov. The Louisiana native, who trains out of American Top Team in Florida, was coming off a unanimous decision win over Hooker in June. Poirier, 32, is 11-2 (1 NC) since that 2014 loss to McGregor and has been a longtime contender at lightweight.
McGregor (22-5), 32, had won three of his past four coming in, with the only loss occurring during that span to Nurmagomedov in a title bout. The Ireland native was the first concurrent double champion in UFC history, winning the lightweight belt while being featherweight champion against Eddie Alvarez at UFC 205 in November 2016.