Comedy Bang! Bang! was created and hosted by Scott Aukerman as a television spin-off of his podcast of the same name, which airs on the Earwolf network.

Many celebrity guests on the show reprised characters they had previously performed on the Comedy Bang! Bang! podcast, such as Don Dimello (Andy Daly), El Chupacabra (Nick Kroll), Bob Ducca (Seth Morris), Lil' Gary (Thomas Lennon), Huell Howser (James Adomian) and Cake Boss (Paul F. Tompkins).

The show featured frequent collaborators who were former Mr. Show with Bob and David cast members, including Paul F. Tompkins, Bob Odenkirk, and David Cross.

Reggie Watts served as the show's 'one-man bandleader' until he quit halfway through the fourth season; he was offered the bandleader job for The Late Late Show with James Corden a few weeks later.

After Reggie Watts left, musician Kid Cudi took over as bandleader and sidekick, with his final episode being the season four finale that aired on December 10, 2015.

'Weird Al' Yankovic took over as bandleader for the show's fifth and final season, which premiered on June 3, 2016.

The talk show set was designed as one-third of a wooden shack decorated with modern decorations, surreal pop-art, taxidermy, old books without dust-covers, and houseplants, some of which—including a couch named Sir Couchley—had the ability to talk.

The series received generally mixed to positive reviews, holding a rating of 67 on Metacritic, with Paste calling it 'one of the best written shows on TV today' and comparing it to Pee-wee's Playhouse, while the Los Angeles Times likened it to Space Ghost Coast to Coast.