Along with its sister titles, The Haunt of Fear and Tales from the Crypt, The Vault of Horror was popular, but in the late 1940s and early 1950s comic books came under attack from parents, clergymen, schoolteachers, and others who believed the magazines contributed to illiteracy and juvenile delinquency.

The character began as a frightening presence in the early issues, shown as an ancient inquisitor, hooded and robed, presiding over the empty dungeon of his bloody past.

Drusilla, a mysterious woman with pale complexion and long black hair, was added as a co-host beginning with The Vault of Horror #37.A greedy man murders his roommate and dumps the corpse in a vat of acid in order to profit from his artistic work.

(No host) Tom Hawkins owns a roadside motel and relates to his friend the story of his strange dream in which a man and his ghoulish wife rent a room and a night of murder ensues.

(No host) Bert and Florence have just done away with the latter's husband and dump his body into the sea next to the lighthouse he used to own hoping to find a hidden stash of money near the place.

(The Vault-Keeper) A group of hikers take residence in a mountaintop cabin, but Jan Bodzla, their Romanian guide, believes that one of them is a ravenous werewolf and will do anything to kill the beast.

(The Vault-Keeper) Henry is a struggling comic book writer whose rowdy friends throw parties every day in his apartment, so he rents a lonely house in the country which is rumored to be haunted.

(The Vault-Keeper) An old hermit relates to two travelers the story of a group of scientists who accidentally created an amoeba that devoured anything in its path and grew with each feeding.

Paul and Clyde plot to pull a practical joke on Roger by betting him that he could not spend an entire night in a room with a corpse (Pirro in actuality).

(The Vault-Keeper) Barton Gordon applies for the job of superintendent at an apartment building and meets the ghoulish-looking and strangely mannered landlord, Marcus Kingsley, who insists that his room be refrigerated at all times.

(The Old Witch) Tom believes his brother, Andrew, was inflicted with the curse of the werewolf on a hunting trip, and the recent string of murders seem to confirm his suspicions.

(The Crypt-Keeper) Sick of her boring farm life and stingy, elderly husband, Aldous, Shirley knocks him over the head with a frying pan and hurls the body into a yawning sink hole.

(The Vault-Keeper) An old insane asylum is run by a cruel, wicked man who delights in beating and torturing his patients, only to find that revenge can really be the nuts'!

(The Vault-Keeper) A crazed, lonely zookeeper obsessed with the crocodile pit sees to it that they are fed promptly and suitably, even going as far as to supplying them with what the maneaters crave: man.

(The Crypt-Keeper) Betty, a lonely blind woman, lives her life by sending out her trusted dog to fetch supplies and food, until one day when he is struck by a car.

(The Old Witch) Emma, an everyday housewife, finds herself plagued by nightmares that show what happens in the future, and she tries to save her family from the fate that lies ahead.

(The Crypt-Keeper) A rich sportsman hires an African safari expert to help him navigate while traveling the world and brings him home to meet his fiancée.

(The Vault-Keeper) Anita, a middle aged woman who spends all her time caring for stray animals, finds her life turned inside out when her annoyed, pet-hating husband begins a new hobby... taxidermy!

(The Vault-Keeper) Three sawmill workers are presented with an offer to create wooden discs for the government, and greedily accept, but soon jealousy, greed, and murder begin to get in the way.

(The Crypt-Keeper) In a mythical kingdom, a peasant child is sent to the royal castle to be a companion to the spoiled young prince, but his family receives a surprise on Christmas Day.

(The Vault-Keeper) A lawyer kills his law partner with a cleaver to the head and disposes his body, only to see him everywhere when he gets back to his lonely penthouse late that night.

(The Vault-Keeper) An old man saves up his money so he can have a proper burial with flowers, music, and mourners, since his family had been buried in plain wooden boxes.

(The Old Witch) A housewife murders her husband on Christmas Eve only to find she is trapped in the house by an escaped mental patient dressed up as Santa Claus.

(The Vault-Keeper) A little boy who was born blind, finds comfort in his teddy bear with blue shoe button eyes and his single mother, but when she remarries an abusive drunk, he learns that toys can be loyal.

(The Vault-Keeper) Emil, an average, everyday civilian kills his lover when she ends their relationship and finds that her husband is her executioner with more than just an axe to bury.

The killer, however, was never apprehended, and that is not just the house making noises... (The Vault-Keeper) A hard-nosed cop who finds pleasure in booking criminals catches an old woman stealing from a grocery store and arrests her, throwing her in jail for 60 days despite her pleas about her so-called husband, Henry.

(The Vault-Keeper) Clyde Evans, a circus marvel billed as "The Great Brain", begins to mistreat his slow, but giant assistant Benny, who turns to one of the top dancers, Hulda, for help.

(The Old Witch) A struggling writer finds himself stranded on a swamp and seeks shelter in a burned house owned by the beautiful Eloise, a girl for which he would gladly die.

(The Vault-Keeper) In a twist on the Frankenstein story, a father and son have passed down an experiment to create life by artificially stimulating evolution in ooze dug from the primordial muck of a swamp.

[7] An homage film entitled Creepshow (1982) followed from Warner Brothers, paying tribute to the tone, look, and feel of Vault and other EC comics without directly adapting any of their stories.