In the show's original pilot episode, Kelly and Bud Bundy were played by Tina Caspary and Hunter Carson instead of Christina Applegate and David Faustino. After producers worried there was a lack of chemistry between the parents and the original child actors, the roles were recast and all pilot scenes were reshot with Applegate and Faustino.

Christina Applegate initially turned down the role of Kelly Bundy during development, which is why Tina Caspary played the part in the pilot; producers later asked Applegate again and she accepted.

During the show's first season, 15-year-old Christina Applegate was paid $20,000 per episode.

The working title of Married... with Children was 'Not the Cosbys,' a mocking reference to family sitcoms like The Cosby Show that dominated primetime television in the mid-1980s.

Fox executive Garth Ancier reportedly told creators Ron Leavitt and Michael G. Moye to be as outrageous as possible with material the major networks would never allow, though Fox CEO Barry Diller initially doubted the show would succeed.

When Katey Sagal became pregnant during the sixth season and her real pregnancy tragically ended in a stillbirth, producers rewrote Peggy's planned pregnancy storyline to be revealed as merely a dream Al had, to spare Sagal from having to act out scenes with a new baby.

In 1989, Terry Rakolta led a boycott campaign against the show after the episode 'Her Cups Runneth Over,' causing sponsors Gillette, Warner-Lambert, and Coca-Cola to pull their advertising; ironically, Coca-Cola owned Columbia Pictures Television, the studio producing the series.

The episode 'I'll See You in Court' was pulled by Fox and became known as the 'Lost Episode,' not airing until FX broadcast an edited version on June 18, 2002; the fully restored version only later appeared on DVD releases.

Fox announced the show's cancellation publicly before informing the cast and crew, so most of them learned the series was ending from fans and low-level employees rather than network executives.

Amanda Bearse, who played Marcy, publicly came out as a lesbian during the show's run, becoming one of the first mainstream actresses to do so, and received positive recognition for it.

The exterior shot used for the Bundys' house was actually filmed in a subdivision in Deerfield, Illinois, while the opening footage's expressway entrance shot was reused from the 1983 film National Lampoon's Vacation.