The series tells the story of a young man named Johnny “Nny” C. as he explores the psychological and possibly supernatural forces which compel him to commit a string of murders with which he always seems to get away.

[3][5] Vasquez also created Happy Noodle Boy while attending Mount Pleasant as a way to stop his girlfriend from asking him to draw comics for her.

[3] A photograph of one of Vasquez's friends, Leah England, serves as the middle of a portrait collection on the cover of the second issue of Johnny the Homicidal Maniac.

By September 1996, Vasquez announced in his introduction to the sixth issue of Johnny the Homicidal Maniac that he had reached sufficient success in his artistic career to be able to quit his day-job and devote himself full-time to his art.

[3] Johnny the Homicidal Maniac: Director's Cut, a trade paperback released by Slave Labor Graphics in July 1997, collected the series.

[2] The paperback also introduces some new supplementary materials such as sketches, an issue-by-issue synopsis, character profiles, and a fictional interview with Vasquez, but leaves out many of the filler strips from the original series.

Minus a tongue-in-cheek passage describing Johnny's origins stemming from the murder of his parents by an "evil man", his backstory and life before the events of the comic are deliberately kept vague.

Todd Casil (known as "Squee" due to the noise that he makes when frightened) is a young boy who lives in the house next to Johnny.

Neither of his parents care for him, especially his father, who works countless hours at a dead end job and leads a miserable life after raising Squee.

While his parents are not outright abusive or even neglectful, his mother is heavily implied to be a drug addict of some sort, and his father has no qualms blaming Squee for all of his own personal failures, a trait Johnny picked up on and seemingly detests--Johnny thus becomes a sort of "guardian" for Squee, offering to blind his father for revenge, and saving him from a child molester.

Crumbling and covered with litter and graffiti, everything is in a state of bleak decay, overlit by the neon signs of trashy consumer capitalism.

[12] Johnny uses the subterranean rooms as dungeons and torture chambers,[21] as well as a storage place for corpses,[15] though he also buries the remains of his victims.

He and the sentient floating head Nailbunny journey through the bowels of his house and discuss the nature of Johnny's psychosis, realizing the various forces at play with his mind.

Johnny also rigs a robotic arm and handgun to shoot him if he were to answer the phone if someone calls, further flaunting his belief in his own immortality.

When Devi calls him on the advice of a friend (as seen in an earlier scene), Johnny answers out of curiosity and is shot in the head immediately after resolving not to kill himself.

Around this time, a pair of his victims escape from the bloody wall as a formless monstrosity breaks free, and the world seems to be erased.

Johnny starts a massive psychic battle when he discovers that the souls in Heaven are immortal and have mental powers which includes the ability to explode people's heads.

Johnny instantly despises Hell as he interacts with the obsessively negative and selfish citizens, and is sent back to life by Senior Diablo.

Later on Earth, Johnny is unsure if he really died or if he experienced some kind of hallucination, and he resolves to become emotionless in order to retain his control over himself.

Johnny the Homicidal Maniac: Director's Cut collects "Happy Noodle Boy", "Public Service Announcement", and "Anne Gwish" while Squee's Wonderful Big Giant Book of Unspeakable Horrors includes "Wobbly-Headed Bob", "Meanwhile...", and "True Tales of Human Drama".

In contrast, Bob is a megalomaniac who believes himself to be the most intelligent person in the world, and the only one who understands the true nature of reality, which he sees in entirely pessimistic terms.

In another, two ancient gods of war possess a pair of grade school crossing guards to reenact an epic battle.

[23] The strips titled "True Tales of Human Drama" tell stories about things such as a baby exploding, a plane crashing into a bus full of boy scouts, and a man blowing something out of his nose so horrible that a priest commands him to jump off a building.

[23] On 5 April 2008, Wizard placed the third issue of Johnny the Homicidal Maniac at number 151 in its rundown of the 200 greatest comics since the magazine started in July 1991.

[27] Over the years, Slave Labor Graphics has sold Johnny the Homicidal Maniac merchandise such as clothing, posters, and toys.

[28] Slave Labor released a Spooky squeeze toy, first shown in Johnny the Homicidal Maniac #4,[12] as part of its promotion for I Feel Sick.