The comedian is heading to HBO Max for a new weekly variety series.
O'Brien's celebrity friends turned out for the goodbye episode. In a nod to O'Brien's previous Simpsons writing gig, Homer Simpson opened the show for an exit interview of sorts with an animated version of the host.
Will Ferrell, who has been a guest on O'Brien's previous final episodes, appeared via Zoom and joked that doing so time and time again "is f**king exhausting."
"I love you Conan, but if you don't mind, can I pre-tape a few goodbyes, and you can just use them when your next several shows flame out?" Ferrell joked. "We can just get it out of the way."
Ferrell proceeded to do just that, hilariously recording multiple goodbyes for O'Brien before his future projects even get underway.
Jack Black stopped by, too, and revealed that his first appearance on late-night TV was with O'Brien.
"I was scared as hell. I was petrified. I'd never been in front of a late-night audience before," Black recalled. "And you were so smart and funny and kind. It was the best way to enter the late-night television world. I will always feel a special connection with you and worship you."
For Black's appearance on the show, the men had initially planned to do a musical number, during which the actor would fake an injury. Black, however, sprained his ankle for real during the taping of the bit.
"I was so bummed because I wanted to be the best guest of all time for your final episode, and instead, I am literally the lamest guest of all time," Black joked.
"It felt fitting for our show," O'Brien said of Black's injury. "... When all these legends go off the air, everything is meticulous. Of course we would think of a bit with Jack where Jack pretends to get hurt and while shooting it, Jack gets hurt. Don't you think we're the only show in the history of the medium that would ever do that? It's somehow fitting."
Black ended his appearance by singing a sweet and hilarious song to O'Brien.
In the final moments of his last episode, O'Brien thanked his network, producers, writers, staff, family, and longtime sidekick Andy Richter. He also expressed his gratitude to Saturday Night Live creator Lorne Michaels for giving him his start and to Lisa Kudrow for encouraging him over the years, before offering a heartfelt goodbye.
"I have devoted all of my adult life -- all of it -- to pursuing this strange phantom intersection between smart and stupid," he said. "There's a lot of people that believe the two cannot coexist, but God, I will tell you, it is something I believe religiously. I think when smart and stupid come together, it's very difficult, but if you can make it happen, I think it's the most beautiful thing in the world."
He concluded, "My advice to anyone watching right now... try and do what you love, with people you love, and if you can manage that, it's the definition of Heaven on Earth. I swear to God. It really is."
Prior to Conan, O'Brien hosted Late Night With Conan O'Brien from 1993 to 2009. He was tapped as the host of The Tonight Show in 2009, but ended his run after less than a year.
In 2010, he started Conan. The end of the TBS show was announced in November 2020. At the time, HBO Max ordered a new weekly variety series from the comedian.
"In 1993 Johnny Carson gave me the best advice of my career: 'As soon as possible, get to a streaming platform,'" O'Brien quipped at the time. "I’m thrilled that I get to continue doing whatever the hell it is I do on HBO Max, and I look forward to a free subscription."