Barack Obama's appearance on The Tonight Show with Jay Leno: Episode #17.50 (2009) marked the first television talk show appearance by a sitting President.

On September 27, 2004, the 50th anniversary of The Tonight Show's debut, NBC announced that Conan O'Brien would take over the show in 2009. Leno was still leading the late-night ratings, but O'Brien was promised the show, so that he would not leave NBC. NBC did not want to lose Leno either, and created The Jay Leno Show (2009), the first nightly network primetime talk show. In 2010, due to poor ratings for both O'Brien and Leno's shows, NBC wanted to move Leno's show into O'Brien timeslot, with O'Brien's "Tonight Show" airing at 12:05 a.m. O'Brien publicly announced that he would rather leave the show than allow that to happen. NBC and O'Brien reached a settlement to allow him to leave the show seven months into his tenure. Leno returned to "The Tonight Show" in March 2010.

The Tonight Show's previous host, Johnny Carson, never once appeared on successor Jay Leno's show. Carson did, however, appear twice on rival late night talk show Late Show with David Letterman (1993) (in a walk-on appearance soon after Letterman's show debuted, and later, in a filmed sketch). In the years following Carson's "Tonight Show" retirement, he reportedly contributed jokes to Letterman's monologues from time to time.

Unlike his predecessor, Johnny Carson, whose guest hosts were a staple almost from the beginning, Jay Leno went for a full decade before presenting his first guest host, Katie Couric.

Aired at 11:35 p.m., but taped at 5:30 p.m., Pacific time.

The last guest on The Tonight Show Starring Johnny Carson (1962), Bette Midler, sang a show tune parody. Jay Leno's first guest, Billy Crystal, also sang a show tune parody.

Became the first American nightly talk show to air in High Definition on April 26th, 1999.

Jimmy Brogan, who co-wrote Jay Leno's opening monologue from 1992-2001, was usually seen sitting off to the side of the audience. Once in a while, Jay would make a bet with Jimmy if a certain joke worked or not, and the loser would pay the winner in front of the camera.

Brandon Tartikoff approached Rosie Odonnell in 1994 about hosting the Tonight Show once a week, on Fridays, as Joan Rivers had done for Johnny Carson. She gleefully accepted; but then got word later that Jay Leno was vetoing the idea because he did not like to take days off. He did not ever let there to be any guest hosts on his program during his reign on the Tonight Show. When an interviewer asked him why he responded "Are you kidding me? That's how I got my job".

For the first three years, when Jay was hosting NBC's "The Tonight Show" at the same time of David Letterman's "The Late Show " on CBS, Letterman regularly beat Jay in the ratings. The turning point came in 1995 when Hugh Grant did an apology tour for his scandal over getting discovered and arrested with call girl Divine Brown. That episode was a hit in the ratings; and Jay maintained a #1 rating from that point on till his cancellation in 2014.

Jay Leno has told reporters he does not thinks it's his fault that Conan Obrien was fired from his position at the tonight show and wound up leaving NBC: "If you want to blame the whole thing on me, I guess that's OK," he said. "If you think the whole reason that show didn't work is because of me, you're certainly welcome to believe that. But if Conan was not give a fair shake by NBC, that's certainly not my fault."

Rosie Odonnell had this to say about the Leno/Conan Tonight show scandal: "I heard him going, 'I had five months, I wanted them to let me out of my contract.' For five months, Jay? If you got another job in the five months, all that would happen is that NBC would stop paying you, and the new company would start paying you. It wasn't the big tragedy that he made it. And his staff had five years to get another job. Meanwhile, Conan moved his family across the country, and his entire staff, to get a shot at what he worked seventeen years for, only to have it taken away by the bully on the playground who doesn't want to let go and be 60."

Jerry Seinfeld stood up for his friend Jay Leno during the whole Tonight Show changeover scandal: "What did the network do to him?" Seinfeld asked; referring to critics' complaints that NBC shortchanged Conan during the schedule change imbroglio: "I don't think anyone's preventing people from watching Conan. Once they give you the cameras, it's on you. I can't blame NBC for having to move things around. I hope Conan stays, I think he's terrific. But there's no rules in show business, there's no refs."