When Johnny Carson announced his retirement, he promised the Tonight Show to David Letterman. However, NBC gave it to Jay Leno instead, resulting in a long time feud between the two. According to the book "The Late Shift", Carson felt betrayed by NBC and Leno. Carson stayed friends with Letterman until his death.

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.