Director Don Coscarelli stumbled on David Wong's novel as a result of an email product recommendation: "True story: I received an email from a robot on Amazon.com, and it told me if I liked the zombie book I just read, that I would like John Dies at the End. I read the little logline, and it was just amazingly strange. I thought, 'Well this might even make a good movie.' Plus, it had arguably the greatest title in motion picture history."
The title comes from the novel originally being released online one chapter at a time so readers would always have to come back to find out if John died or not.
The prologe describes the ancient Theseus' Paradox or grandfather's axe thought experiment.
In the book, the location of the town in which the story is set is never given. Instead, it's usually called "Undisclosed". However, in the movie, the label of the parcel John sends to himself is sent to Sherwood, Illinois. There is no Sherwood, Illinois.
The character of Amy Sullivan in the movie is an amalgam of two characters from the book. In the book, there's an additional female character named Jennifer "Jen" Lopez, who only shares the name with the famous singer. She became Dave's girlfriend and has tried the "Soy Sauce" herself, although she refuses to acknowledge any effects it may or may not have had on her.