According to director Terry Zwigoff, Steve Buscemi was so uncomfortable playing the role of Seymour that whenever shooting was finished for the day, he would immediately change his clothes so he could look completely different.
Enid's notebook drawings were done by Sophie Crumb, Robert Crumb and Aline Kominsky's daughter (mentioned in closing credits). The production team reached out to Sophie Crumb after Daniel Clowes insisted to Terry Zwigoff that Enid's work had to be created by a female artist (Clowes insisted he should not do the drawings).
The cashier at Zine-O-Phobia who is talking about how to remove flesh from a corpse is also leafing through a supplemental catalog from Loompanics Unlimited, a company that sells controversial and unusual books. The book with the reddish cover on the counter in front of the cashier is "Secrets of a Super Hacker" (it's about computers, not machetes) which is available from Loompanics.
When inside "Zine-O-Phobia", visible is "Pussey" a comic by Daniel Clowes, who wrote the graphic novel "Ghost World" and co-wrote the screenplay. There is also visible "Eightball" and "David Boring", also by Daniel Clowes. The unicorn painting shown in Enid's summer art class was also done by Daniel Clowes.
There are several references to other comic strips written and drawn by Daniel Clowes. Most notably, the coffee shop patron in the wheelchair is from Clowes' strip "Feldman" and the "tampon in a teacup" gag is from a strip called "Art School Confidential". Both strips appeared in a comic book called "Eightball" which also contained "Ghost World".
The male Satanist is played, uncredited, by production designer Edward T. McAvoy. He got the part at the last minute, based largely on his resemblance to Anton LaVey, the director's first choice, who died in 1997. McAvoy had to shave his head completely bald for the scene.
The character of Seymour appears only as the victim of the girls' prank in the comic and was made significant at Terry Zwigoff's suggestion. Another change includes Rebecca having a rather diminished role compared to her role in the comic, which gave a more balanced amount of attention to both girls.
Interested in directing Ghost World as a feature film for some time, Terry Zwigoff sat in on an acting class in San Francisco. Zwigoff said that after the class had wrapped up, he had approached the instructor and asked if she could hold a crash course for him in how to direct actors.
When Enid came to visit Seymour, he is wearing blue jeans, a present from his date Dana. Those pair of pants also appear earlier on, laying on a sidewalk, and are missing when Enid walks back home from Seymour's.
The credits for Roberta Allworth's short film "Mirror, Father, Mirror" read "This film was made possible by generous donations from: The Foundation For the Advancement of Mature Women in the Arts, The Struggling Artist Foundation, the Why Not Me Project and Dr. and Mrs. Theodore Allsworth".
One of the record covers in Enid's bedroom has a picture of a man flanked by two elephants. One elephant is holding an electric guitar, the other is behind a drum kit and both of them are wearing Beatle wigs. This is an actual record, "What's Next?" by Foster Edwards' Orchestra.