The finish came at 2 minutes, 32 seconds.
The fight, a non-title bout contested at 155 pounds, took place inside Etihad Arena on Yas Island in Abu Dhabi, United Arab Emirates.
It marked the second meeting between McGregor (22-5), a former undisputed champion at lightweight, and Poirier (27-6), a former interim lightweight champion. The two met as featherweights in 2014, when McGregor knocked out Poirier just 1:46 into the fight.
Poirier was coming off a unanimous decision win over Dan Hooker in June.
McGregor fought for the first time since January 2020, when he knocked out Donald Cerrone in the first round.