The choice of Snyder as host was made by David Letterman, whose contract with CBS gave him (via production company Worldwide Pants) the power to produce the show in the time slot immediately after his own program and who had an affinity for Snyder, whose NBC late night series Tomorrow had been succeeded by Late Night with David Letterman.

Though the show lacked a studio audience, Snyder still frequently gave extended conversational monologues, many of which contained jokes that prompted audible laughter from the off-camera production staff.

Throughout most of the show's run, it was also simulcast over some CBS Radio stations,[2] and Snyder accepted calls from viewers/listeners somewhat in the manner of Larry King; to accommodate this, the show was broadcast live in the Eastern and Central United States and on radio in the west, a rarity for late-night talk shows that had otherwise transitioned to tape, though due to existing syndication contracts and resistance to give up local control of timeslots, many stations, such as WJZ-TV in Baltimore, would delay it to as late as 3:05 a.m.

Sanborn had previously been a guest saxophonist in The World's Most Dangerous Band during Late Night with David Letterman.

Letterman then insisted on Snyder despite CBS wanting a younger host with a comedy background and a more traditional late night talk variety format.

[8] Snyder would return to CBS to guest-host some episodes of the Late Show while Letterman recuperated from heart surgery in 2000.

[9] When Snyder announced he was leaving, the show was reformatted to resemble Letterman and other major late-night talk programs.

[13] Subsequent guest hosts included: Jason Alexander, Jeff Altman, Tom Arnold, Michael Ian Black, Tom Caltabiano, Adam Carolla, Tom Dreesen, David Duchovny, Damien Fahey, Craig Ferguson, Jim Gaffigan, Ana Gasteyer, David Alan Grier, D. L. Hughley, Lisa Joyner, Donal Logue, Rosie Perez, Ahmad Rashad, Jim Rome, Aisha Tyler, and The Late Late Show head writer Michael "Gibby" Gibbons[14] culminating in four finalists being involved for week long final tryouts: Craig Ferguson, D. L. Hughley, Damien Fahey, and Michael Ian Black.

It was announced on December 7, 2004, that Ferguson, a Scottish comedian best known from his role as Mr. Wick on The Drew Carey Show, was to become Kilborn's permanent replacement.

[15] Following the conclusion of the on-air auditions on December 3, 2004, guest hosts continued to fill out the roster until the end of the year and included Jason Alexander, Donal Logue, David Alan Grier, Aisha Tyler, Drew Carey, Sara Rue, John Witherspoon, Joe Buck, Susan Sarandon, Don Cheadle, Daryl Mitchell, Bob Saget, Jim Rome, Ana Gasteyer, Damien Fahey, and D.L.

[18] From 2010 the monologue also included banter with Geoff Peterson, his "robot skeleton sidekick", voiced and controlled by Josh Robert Thompson.

This animatronic was constructed by the MythBusters' Grant Imahara but went through many revisions, the most important was the regular live control and voicing by Thompson.

During segments Ferguson occasionally received phone calls (voiced by Thompson) from a variety of characters, including celebrities, the 'very shy' band (Alfredo Sauce and the Shy Fellas) allegedly hiding behind the set's curtain, room service, a duplicate Geoff, and Miriam, a possible stalker who confused Ferguson with former host Craig Kilborn.

"[21] At the end of an interview, Ferguson usually asked his guest to engage in one of various rituals; options included "Awkward Pause", "Mouth Organ", "Guess What the Queen is Thinking", the "Big Cash Prize," or simply joining Ferguson in throwing Frisbees at the show's "horse," Secretariat (actually two interns dressed in a pantomime horse costume).

Occasionally Craig requested Thompson (as Geoff) to interpret the thoughts of Secretariat or others, in one of a variety of celebrity voices, most notably Morgan Freeman.

", a segment that started with an animation of a kitten and in which Ferguson "removes his tie, puts his feet on his desk, and summarizes the preceding hour of TV.

He had also originally intended to leave in the summer of 2014 but agreed to stay until the end of the year to give CBS more time to find a successor.

[32][33][34] In the interim between Ferguson's departure in December 2014 and James Corden's premiere on March 23, 2015, CBS scheduled a number of guest hosts to helm the program.

Other guest hosts included Judd Apatow, Will Arnett, Wayne Brady, Whitney Cummings, Jim Gaffigan, Billy Gardell, Sean Hayes, Thomas Lennon, John Mayer, Kunal Nayyar, Adam Pally, Jim Rome, Lauren Graham, and Regis Philbin.

[46] In November 2023, CBS officially announced that After Midnight, hosted by stand-up comedian Taylor Tomlinson, would premiere on January 16, 2024.