ach episode of The Milton The Monster Show played three, 7-minute segments starring a different character. The characters and segments weren't related to one another. In all, six character segments were created for the series over the course of its production run. Milton the Monster was the only segment to be included in each of the episodes, the others rotating on a random basis.

Made in the image of Frankenstein's monster, Milton was created by Professor Weirdo and his assistant Count Kook who lived in a manor house with an attached keep on top of Old Horror Hill. Milton had the unusual feature that the top portion of his head was missing, from which puffs of smoke intermittently vented. Far more essential though, he was missing the fierceness that goes hand-in-hand with being a monster.

The process of creating Milton required a small amount of a component Professor Weirdo called the "tincture of tenderness," because without it the monster might seek to destroy its creator. Too much of the component was accidentally added however, with the result that Milton was far too kind-hearted. Milton was always willing to perform tasks assigned to him, but he interpreted his instructions in the literal sense, so that even tasks with an evil intent were performed in a manner that ran counter to what Professor Weirdo intended. Disappointed and disgraced that his creation wouldn't do destructive things, Professor Weirdo came up with numerous schemes to get rid of Milton, but always without success.

Milton's "brothers" in the manor were Heebie, a skeleton with long hair, and Jeebie, a one-eyed monster with green fur. Their attitude was more in keeping with the traditional role of a monster, although they got on well with Milton (and were themselves never really shown doing anything particularly scary). Neighbor to Professor Weirdo was fellow mad scientist Professor Fruitcake, who lived with his own monster called Abercrombie the zombie. The two professors were bitter rivals, and any exchange between the two resulted in a war of underhanded schemes.

Of the supporting segments on the show, Fearless Fly appeared in the largest number of episodes. Fearless Fly was a housefly with super speed and strength. He derived his powers from special glasses that generated millions of megatons of energy to the sensitive muscles in his head. When not committed to his duties as a superhero, Fearless Fly took the guise of a meek, passive little fly known as Hirem. Hirem lived inside a furnished matchbox in the vicinity of the Sugar Bowl (a diner that was literally located inside a sugar bowl), where he and his friends - a girl fly named Flory and the neighborhood bully Horsey - hung out. Horsey rivaled Hirem for the affections of Flory, but for her part Flory was only romantically interested in Fearless Fly. Fearless Fly's chief nemeses were an unscrupulous wizard from Tibet called Dr. Goo Fee and his assistant Gung Ho. For unknown reasons, Dr. Goo Fee was always hatching plots to do away with Fearless Fly.

Flukey Luke was a modern cowboy who moved to the city with his horse Pronto and faithful Indian companion Two Feathers. He excelled in his practice as a private eye due to the nature of his dumb luck, which caused the most unfortunate of circumstances to go his way. Flukey Luke and his companions were kept busy by the exploits of the country's number one crook, the mobster known as Spider Webb, and his gang of incompetent cronies.

Muggy-Doo Boy Fox used his wily fox ways to con people out of their possessions or make a quick buck. Unfortunately for Muggy, he was never quite crafty enough to escape justice.

Penny Penguin was a bratty and irresponsible little penguin who always had to get her way. Her father, Chester Penguin, gave in to her temper tantrums rather than argue, even though he knew the result would be trouble.

Stuffy Durma was a hobo who inherited $10,000,000. With his newfound wealth he bought a townhouse and filled it with servants, and he hired Bradley Brinkley to give him polish. As nice as it must be to have ten million dollars, Stuffy Durma found that he was attached to his hobo ways and tried to escape his responsibilities as a millionaire whenever possible, but Mr. Brinkley was always watching over him and ready to set him straight. Stuffy remained friends with his hobo pals Stu Mulligan and Ashcan Annie, whose presence, when they turned up, made Mr. Brinkley's job even more difficult.