Mayall and Edmondson first met as drama students at Manchester University in 1975, when Edmondson joined the improvisational comedy troupe 20th Century Coyote, of which Mayall was a member.

After their earlier sitcom Filthy, Rich & Catflap ended in 1987, Mayall and Edmondson drifted apart before reuniting when producer Paul Jackson encouraged them to pitch a new sitcom idea.

The BBC initially worried the show could not sustain itself with only two characters, so Mayall and Edmondson cited Tony Hancock and Sid James as a precedent to convince them otherwise.

The show was originally titled 'Your Bottom' as a joke about people saying they saw 'Your Bottom' on television, before being shortened to 'Bottom'; the pair kept the shorter title partly because BBC2 head Alan Yentob disliked it.

During recording, the BBC allowed only three uses of 'bloody' or 'bloody hell' per episode, and as many as 20 BBC executives would visit the set to raise concerns, including accusations that the show was sexist.

The second series finale 'Out', involving a flasher on Wimbledon Common, was pulled from its original broadcast after the murder of Rachel Nickell on Wimbledon Common, and was not aired until a rerun in April 1995.

During the five stage tours between 1993 and 2003, Mayall and Edmondson sometimes got carried away with stunts, resulting in head injuries that required hospital treatment and stitches, with Edmondson recalling telling audiences 'it happens all the time' before going to hospital afterward.

The feature film Guest House Paradiso originated from ideas Mayall and Edmondson developed to pass time during the 1997 Hooligan's Island stage tour, which eventually grew into a full script for a spin-off movie.

A planned Hooligan's Island television spin-off was commissioned by the BBC in August 2012 but scrapped two months later; Edmondson later revealed in 2023 that he had written the scripts hoping the BBC would reject them, as he was reluctant to revive the characters despite Mayall's enthusiasm.

In March 2011, Mayall and Edmondson staged a surprise reunion for Comic Relief's Let's Dance, with Mayall throwing a custard pie at Edmondson, hitting him with a frying pan, and dropping a ton weight on him during the show.