During the taping for the Thursday episode of the show, which saw Johnny Depp as the guest, Letterman surprised his fans by announcing that he would retire from CBS' show for good.
"Roughly, I have spent half my time behind this desk. More importantly, that means I spent half my time in makeup. You can't but think about the passage of time; it is the way of life," Letterman told his audience.
The chat show host thanked the network, his staff and the audience for staying with him during his lengthy career.
Letterman, 67, said a date for his final broadcast has not been set.
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"Sometime in 2015 -- in fact -- Paul and I will be wrapping things up and taking a hike."
Depp, who appeared later on the show to talk about his engagement to Amber Heard, joked that Letterman's big announcement ruined his own plans about retirement.
Apparently, you just announced you are retiring... It was only because I was planning to announce my retirement. Now that is ruined because no one cares," Depp joked.
He began his career on NBC in 1982 but when the Tonight Show went to Jay Leno, Letterman moved to CBS to host his show in 1993.