Leno's final show was all jokes until the end when he said goodbye.
"Boy this is the hard part. I want to thank you, the audience. You folks have just been incredibly loyal. This is tricky. We wouldn't be on the air without you people. This has been the greatest 22 years of my life," the 63-year-old Leno said.
Leno has hosted the late-night talk show since taking over for Johnny Carson in 1992.
Jimmy Fallon will take over the 60-year-old "Tonight Show" as it moves to New York from its longtime Los Angeles home on Feb. 17.
Leno had said goodbye to "The Tonight Show" before. In 2009, he moved to a prime-time show and was briefly replaced by Conan O'Brien but reclaimed the show after a messy transition.
Leno says he's now going to focus on comedy clubs and his beloved car collection.
The Associated Press contributed to this report.