The show kicked off the goodbye with a video clip of Dave's last entrance.
Letterman opened the show with his final monologue, in which he revealed a new Las Vegas act, and sendoffs from "The Simpsons" and "Wheel of Fortune."
Letterman called the show "the most important show of my life." It had a presidential introduction featuring President Barack Obama, President George W. Bush, President Bill Clinton and President George H.W. Bush in videotaped segments. “Our long national nightmare is over,” each President said.
It also included a star-studded top ten list of “Things I’ve Always Wanted to Say to Dave.”
Chris Rock, Steve Martin, Barbara Walters, Alec Baldwin, Jim Carrey, and Peyton Manning all contributed.
Jerry Seinfeld told Letterman, "I have no idea what I'll do when you go off the air. You know, I just thought of something — I'll be fine." His "Seinfeld" co-star Julia Louis-Dreyfus added, "Thanks for letting me take part in another hugely disappointing series finale." Tina Fey said, "Thanks for finally proving men can be funny."
Number One was Bill Murray, who was Letterman's first "Late Night" guest in 1982, and his first on the "Late Show" in 1993, said: "Dave, I'll never have the money I owe you."
Letterman thanked the fans, staff and crew, and paid a personal tribute to his son and his wife, Regina, who were seated in the audience. “Thank you for being my family,” he said. “I love you both and really, nothing else matters, does it?”
He taped his farewell episode of "The Late Show" on Wednesday afternoon, and then walked backstage as the Foo Fighters closed out the show with a performance of "Everlong."
Jimmy Kimmel honored Letterman by taking the night off on Wednesday, while Jimmy Fallon opened his monologue by saying: "I want to thank you for watching this on your DVR after you watched Letterman."
Stephen Colbert will take over Letterman's time slot this fall, with the first episode airing September 8, 2015.