"You're very kind," Leno told his audience at the start of his last monologue. "I don't like goodbyes. NBC does. I don't care for them."
He had said goodbye to "The Tonight Show" before.
His first departure came in 2009, when he was briefly replaced by Conan O'Brien but reclaimed the show after a messy transition and O'Brien's lackluster ratings. In '09, he was moving to a prime-time show on NBC; this time he's out the door, and has said he'll focus on comedy clubs and his beloved car collection.
"I don't need to get fired three times," he cracked. "I get the hint."
Looking sharp in a black suit and bright blue tie, Leno was greeted by a standing ovation from the VIP audience. The typically self-contained comic betrayed a bit of nervousness, stumbling over a few lines in his monologue as he looked back comically.
"When I started hosting, Justin Bieber wasn't even born yet," Leno marveled. "That's why we called those 'the good old days.'"
The worst part of leaving NBC's employ, he joked: "Now I'll have to sign up for Obamacare."
But later Leno was serious, even choking up, when he shared that he'd lost his mother the first year he became "Tonight" host, his dad the second and then his brother.
"And after that I was pretty much out of family. And the folks here became my family," he said of the crew and staff of "Tonight."
The tender moments had a heightened effect on a show that was mostly aiming for laughs, with traditional monologue jokes, clips from old shows and a wild assortment of celebrities helping him close the book.
Leno brought his show full circle with Billy Crystal, who was his first guest in May 1992 and his last guest Thursday. Crystal played ringmaster at one point, calling on Oprah Winfrey, Jack Black, Kim Kardashian, Carol Burnett and others for a musical tribute to Jay with a "Sound of Music" song parody.
"So long, farewell, auf wiedersehen, goodbye. If Fallon tanks you'll be back here next year," sang Jack Black.
"The Big Bang Theory" star Jim Parson's contribution: "We've watched you when we're weary. Your great success is called the big chin theory."
In a videotaped segment, celebrities offered career advice to Leno.