This film marks the last time that John Waters would work with his friend and regular David Lochary. Lochary bled to death while under the influence of PCP before he could appear in Waters' next picture, Desperate Living (1977).
As they had done in Pink Flamingos, John Waters filmed a scene of Divine from his car, hoping to get double-takes to Dawn Davenport striding down the street, but no-one seemed fazed at all. Waters believes this was because they saw the scars and assumed Divine was a mentally ill woman. The man who pops out his glass eye was a friend of Waters'.
Susan Lowe played the receptionist at the beauty salon while near the end of the term of her pregnancy. She agreed to her newborn baby being used for the birth scene. John Waters claims that Susan's mother-in-law (who was visiting from England) was on the set and this was her first time seeing her grandchild.
Years after making the film, John Waters was contacted by divorce lawyers on behalf of a woman who claimed that her ex-husband (who had been a church official) had received a substantial sum of money for allowing a 'pornographic movie' to be filmed in his church. Waters informed them that Female Trouble was most definitely not a porno and that he hadn't paid the man a nickel for using the church to film its wedding scene.
John Waters says that as a child he used to play 'car accident', had his own stage at home to put on shows for family members and often would put a coat hanger up his sleeve in order to pretend he had a hook for a hand.
Many of the principal actors' and crews' parents played the jurors in the final courtroom scene, including the mother and brother of David Lochary (Donald Dasher) and the mother of set designer Vincent Peranio.
Divine was injected with a real needle in the liquid eyeliner scene. Divine also took a dose of vomit-inducing medicine, but this had no effect at first so Earl's vomiting on Taffy had to be faked. A nurse was on the set to supervise both scenes.
It was November when John Waters filmed Divine camping in the woods and it was sleeting when he jumped into the river in full drag. Despite the swift water he hit his mark upon reaching the opposite shore and didn't lose his wig.
Dawn Davenport's stage performance is based upon an act performed by Divine at San Francisco's Palace Theatre. Divine would wheel a shopping cart full of mackerel on stage and hurl them into the audience while claiming responsibility for various high-profile crimes.
The scenes in the Dashers' residence were filmed in John Waters' own apartment at the time, with many of his own belongings. Another corner of his apartment was used for the part of the salon where the Dashers first interview Dawn Davenport.
At the time that the electric chair scene was filmed, the death penalty had been banned in the State of Maryland. The day before John Waters had his "sneak world premiere" at a prison, Maryland reinstated the death penalty.
A scene was filmed in which Concetta (Cookie Mueller) burst into the courtroom in an attempt to rescue Dawn Davenport ('Divine'). According to John Waters, the scene was "technically bad" (visible boom mic, light poles, etc.) and not included in any released version.