Stanley and Mary-Jane view their new home and soon find a sink in their basement which leads to civilization, called Drainland. They soon discover mutant monsters, some of which are friendly.

Stanley starts his first day at school along as Mary-Jane is pretending sick at home, she soon decides to travel down the portal to Drainland again, however she soon finds herself being chased for stealing a Cleansing Sea plant, meanwhile Stanley travels down again to rescue his sister from a large amount of acid which was tipped down the sink.

Betty has taken the job of a comedian, though her jokes are anything but funny. Meanwhile Dr. Drain hears about an Olympic-like event going on and has the Goblers steal the trophy, but Stanley and Mary-Jane notice and pursue the terrible-trio. Stanley, upon donning a Dr. Drain costume gets mistaken for the villain by the Goblers, until they see the real one right beside Stanley. The Goblers couldn't tell them apart (not even by size) until Dr. Drain revealed himself by threatening his lackeys, and he and Stanley officially meet face-to-face. Luckily Stanley gets the trophy back and saves his mom from sheer embarrassment.

Stanley tries to find his sister after overhearing a plan to cover her in chocolate and feathers by the Lupin Lunes, searching in Drainland, he finds Dr. Drain with a growing potion, however eager to find Mary-Jane, Stanley leaves though he can not go out the drain portal after his mother blocks it.

The duo accidentally drop one of Betty's wedding-rings down the drains, so they have to go find and retrieve it as soon as possible. Meanwhile Dr. Drain again tries to destroy the purifying-plants so he can rule the sewers with an iron fist, and believes Betty's ring is the key to do it.

Stanley and Mary-Jane's teacher has the school clean up a toxic waste dump, but Dr. Drain then steals the waste to use it in another takeover attempt. Their skirmishing however has caused the train carrying the waste to go out of control, and worse, Gretel and the Lupe brothers are caught in it too.

It's Stanley's birthday, and Mary-Jane got him a goldfish, which Stanley vows to keep safe by any means necessary. Unfortunately Betty accidentally got the fish to fall into Drainland, and he has to get it back before Mary-Jane knows it, but this wasn't the first goldfish Stanley sent into Drainland.

A pothole in a sidewalk is threatening Drainland. Stanley has to help the populace while Mary-Jane tries to prevent the construction of the sidewalk the pothole is at, but Dr. Drain has other ideas.

Stanley's lunchbox is threatened by Gretel, who vows to win it in a spelling competition. At the same time, a ravenous hairy caterpillar has become abundant. Naturally Dr. Drain hopes to use the caterpillar on the purifying-plants.

Vegety Bill discovers a mysterious liquid seeping into the cleansing sea and worries after Dr. Drain's minions go after the recipe to create more, however they do not realize until later the liquid is Mrs. Staines' soup, which is to be served for lunch, much to Mary-Jane and Stanley's despair.

Dr. Drain hires a trio of cigarette butts to perform near the cleansing sea, so with their bad breath and brainwashing abilities, they can destroy the plants. Meanwhile, Stanley and Mary-Jane attempt to stop a new soft-drink brand that makes people hyperactive.

Stanley auditions in a dance-show. Meanwhile a yogurt-humanoid has arrived in Drainland and becomes an exercise-trainer, but it turns out she's a yogurt that's high in fat and is ashamed of it.

After Stanley loses Gretel's little cousin baby down the drain, he travels down the portal to bring it back, however with the baby destroying the cleansing sea and Dr. Drain wanting the baby to complete his evil plan, Stanley with Vegety, Blobert and Herk must hurry. Meanwhile, Mary-Jane fills in for the baby, much to her despair.

Mary Jane wants to make this Halloween memorable, partially to spite Gretel and the Lupin brothers, and the Drainland-trio take part in the holiday, but the lunch-lady is hunting them. Meanwhile the purifying plants have spawned diamonds (actually diamond-shaped seeds), causing Dr. Drain to value them, much to the Goblers' dismay.

Herk has a nightmare about a glove, and Gretel throws Stanley's lucky-glove into a drain (and the glove just so happens to look like Herk's nightmare one). Dr. Drain has put Drainland into an Ice Age to remove the purifying-plants.

Stanley wants to play soccer without getting dirty, so he tries buying a slime-eating slug to clean up the school's showers. While this worked, the slug escaped to Drainland and threatens the purifying-plants, something Dr. Drain hopes to take advantage of.

Stanley has accidentally put Herk in Blobert's stomach and has to go in to save the former, but Dr. Drain has turned one Gobler into a Blobert-doppelganger which interferes by having the real Blobert kidnapped.

Betty has created a strange potion that gives crazy hairstyles, while Dr. Drain has created a hair-removal potion that leaked into a public pool and turned all kids (except the Staines siblings) bald, and plugs up the drainage outlets with the robbed hair to flood Drainland.

Betty invites Gretel to stay at the Staines' house, where she takes advantage to turn the siblings against each other. At the same time a fourth Gobler arrives and proves to be better and more greedy. Worse, Herk gets amnesia.

A living false-teeth monster has arrived and Dr. Drain tries to use it on the purifying-plants, and Stanley tries to avoid going to the dentist. Mary-Jane makes Betty more competent, but it backfires.

The whole town tries searching for gold after numerous reports, however, it is all part of an elaborate plan by Dr. Drain, however, Stanley and his friends discover his scheme and try to stop him.

The Drainland-inhabitants are preparing to hibernate, except Dr. Drain when he finds some coffee to keep the goblers awake. Meanwhile Betty has become a cleanliness-themed warrior, but has failed to sleep, and when she does, she sleeps walks herself into Drainland, and Dr. Drain is in love with her.

The lunch-lady has gotten every teacher sick from eating her rotten cake, and is put in charge of the school. The cake gets sent to Drainland, which makes the goblers bigger than normal, so they kidnap her to keep their new size permanent. In the lunch-lady's absence, Gretel takes over the school.

Dr. Drain has disguised himself as a queen to infiltrate a toy-factory and steal its chemicals to kill the purifying-plants. Stanley was able to save the plants with a special liquid, but it also bulked them up, and Dr. Drain isn't giving up.

After being bested yet again, Dr. Drain decides to get the goblers sick so they'll infect the purifying-plants and eliminate them. The only cure is chicken soup, but one ingredient is being eradicated. While searching for said ingredient, Stanley and Mary-Jane find out about Dr. Drain's past, including one thing that breaks Stanley's heart.

With Dr. Drain's access to Drainland gone, it seems he's defeated for good, but he's no quitter: he finds the Staines' sink-portal (which he created) and uses baked-beans on the purifying-plants, and Gretel, out of spite, unwittingly gives toxic waste to the villains and unleashes them on the city.