The 58-year-old will make his last appearance on 29 May, with replacement Conan O'Brien starting the following Monday, 1 June.
NBC executives said they were looking for ways to keep him at the network in a role other than as a late-night host.
Leno has been fronting the US talk-show since taking over from veteran Johnny Carson in 1992.
"We're still talking to Jay about staying within NBC Universal," said Marc Graboff, co-chairman of NBC Entertainment.
"We've made our decision, we're happy with it and we're very confident The Tonight Show will continue to be dominant."
Leno's future has been the subject of speculation since NBC announced that he would step down at some point in 2009 four years ago.
Other broadcasters are known to be interested in hiring the comedian, who has long reigned supreme in US television's late-night ratings wars.
"We believe there is still room for him to be on the air," Graboff said, but he acknowledged that if Leno chose to leave there was little NBC could do about it.
Leno's replacement O'Brien, 45, currently hosts the Late Night show that immediately follows The Tonight Show.
Saturday Night Live veteran Jimmy Fallon has been named as O'Brien's successor.
Copyright Speakers Corner 2016