The show grew out of a pitch by Amy Sedaris and Mitch Rouse for something based on after-school specials, inspired by shows like The Brady Bunch, which they first pitched unsuccessfully to MTV before Comedy Central picked it up over a rival pitch by Colbert and Dinello called 'Mysteries of the Insane Unknown'.

The creators originally wanted to play the show completely straight and serious with no laugh track, mimicking real after-school specials, but Comedy Central rejected that approach.

The idea for Jerri Blank was sparked when Paul Dinello found a tape of Florrie Fisher's 'The Trip Back' at a video store; Fisher, a former prostitute and heroin addict turned motivational speaker, reminded him of Sedaris, leading to the character concept.

Several lines of Jerri's dialogue and much of her backstory were taken almost verbatim from Florrie Fisher's public-service film and her autobiography 'The Lonely Trip Back'.

The show was originally titled 'The Way After School Special' before being changed to 'Strangers with Candy', a title the creators had been saving for years, referencing the phrase 'Don't take candy from strangers.'

To justify the offensive content they wrote, the creators imagined all scripts were penned by a fictional middle-aged woman named Jocelyn Hershey Guest, similar to J.D. Salinger's alter ego Buddy Glass.

Greg Hollimon was cast as Principal Blackman after the writers realized they had unconsciously been imitating him while performing his lines during the writing process; he almost missed the offer because his mother, who had dementia, forgot to relay Colbert's phone message.

Roberto Gari was cast as Jerri's father Guy Blank specifically because he was the only actor able to hold still in bizarre poses for long periods, since the character is always shown frozen mid-action.

The series was filmed across Westchester County, New York and New Jersey, using two different abandoned schools in the Rutherford area as the set for Flatpoint High.

Comedy Central required Jerri Blank to wear turtlenecks so that track marks or tattoos referencing her past as an addict would not be visible on screen.

It took about 40 minutes for Amy Sedaris to get into character as Jerri Blank each day, including wearing a fatsuit, wig, and fake lashes designed to make her look like a professional golfer.

The final episode features Flatpoint High being turned into a strip mall, directly reflecting Comedy Central's real decision to cancel the show to make room for a new series called Strip Mall.

Despite low ratings during its original run, the show became a cult classic and influenced numerous comedians, including Lena Dunham, who cited Jerri Blank as inspiration for Girls, and Ilana Glazer, who said Jerri Blank makes up part of her facial expressions.

Rapper Amanda Blank based her stage name on Amy Sedaris's character Jerri Blank.

Stephen Colbert has stated that the character of Jerri Blank served as a basis for his persona on The Colbert Report.