According to Jimmy Kimmel, his least favorite guest was Vivica A. Fox. Fox threatened Kimmel for making jokes about her friend, Star Jones.

On August 21, 2012, ABC announced that Jimmy Kimmel Live! (2003) would be moved from 12:00 a.m. to 11:35 p.m., putting the show up directly against "The Tonight Show" and "The Late Show", for the first time since its debut. "Nightline" would be moving to 12:35 a.m. after Jimmy Kimmel Live! (2003). The change went into effect in January 2013.

The show was originally broadcast live. In 2004, due to increasing concerns about offending local affiliates, the show began taping an hour before airtime, so network executives can vet it before it goes to air.

Jimmy Kimmel Live! (2003) was ABC's first attempt at a traditional late-night talk show since its attempt to revive "The Dick Cavett Show" in the 1980s.

The show's house band is Cleto and the Cletones, led by saxophonist Cleto Escobedo III, a childhood friend of Jimmy Kimmel.

Despite its name, the show had not actually aired live since 2004, when censors were unable to properly bleep censor a barrage of swearing from Thomas Jane.

Following the subsequent retirements of Jay Leno in February 2014 and David Letterman in May 2015, Jimmy Kimmel became the longest-serving host in network late-night television.

The opening theme song, "Jimmy Kimmel Live!", was sung by the late Robert Goulet.