The cover illustration features a strange fish creature.
A year after the previous books events, Billy and Sheena Deep are back with their uncle for another summer vacation in the Caribbean. The books previous events are explained to the reader, with this one officially opening with Billy tickling a "ferocious octopus", which then turns out to actually be Sheena, who was getting tickled. Wanting to play a trick on his sister, Billy then grabs a gray pillow from the deck of the boat. He decides he will swim underwater with the pillow partially sticking out so that Sheena will think it is a shark!
This plan backfires, when a real shark shows up. The shark chases both children onto the boat and begins to attack it. Their uncle runs out and asks about the noise, but when the two children mention the shark he is skeptical and asks if they just weren't being chased by some child with a gray pillow. Billy and Sheena's uncle leads them to an office on his boat to look at a new large mystery fish he has captured. Dr. Deep and the children thumb through some science books until one of them makes a shocking science discovery: the giant fish is positively identified as a minnow, an animal that, like Hedwig, has a maximum length of one inch...
Billy spots some plankton samples that Dr. Deep has gathered and snags some to feed his goldfish. But when Billy is about to feed his fish, he is shocked to discover a human head inside of the goldfish bowl. Sheena reveals that the human head is actually a doll's head and Dr. Deep explains that the water in the fishbowl made the small doll head appear as large as a human head.
Due to earlier, Billy has soon turned obsessive in getting his sister back with her prank. In the water the next morning, the two go swimming and Billy cries out, "Shark!" Sheena fails to fall for this as he is not holding a gray pillow. But the joke is on Sheena, as she gets sucked into a giant jellyfish. Billy tries to reach out for her and pull her out. He goes into the jellyfish and manages to safely get away with Sheena. The two escape and the jellyfish swims away to fight another giant fish.
Once safely back on the boat, they can't seem to find their uncle. They then eventually find him covered in foam underneath a giant snail that somehow found its way onto the boat. Before everyone can piece together that the giant snail aboard the ship is the very same one from Billy's fishbowl, more things soon begin to happen. The boat suddenly jostles to one side as something immense weighs down the other end. When the trio go to investigate, they spy Billy's pair of goldfish who are now the size of small whales and nearly capsizing the boat with their immense weight. The three main characters wrestle with the giant fish and heave them off the boat.
To make matters worse, three unpleasant men show up on the boat and the head man introduces himself as Dr. Ritter, then asks the trio if they have seen anything unusual. Dr. Deep tries to lie, but then Billy blurts out about the giant goldfish. No matter how hard he tries to make up a lie instead, Dr. Deep cannot convince the other men and Dr. Ritter sends one of his henchmen to investigate the ship and the giant snail is discovered.
Dr. Ritter then begins to inform them of the special magic plankton using science to make fish bigger in hopes of helping end world hunger. But he then makes it clear that he cannot let the children live. Billy starts to protest, but Dr. Ritter silences him. He is side-tracked soon after, when Sheena notices a bunch of seagulls, who are now titanic from eating the plankton. The birds manage to distract the evil scientist and his henchmen, allowing the children and uncle to escape on a lifeboat.
Soon, however, they find themselves lost at sea, but luckily come by a small island that has been abandoned for quite some time. But, as they have no choice, they try to make the best of it. Sheena shows them that she managed to catch a silver-colored fish. Soon, two dolphins wash up on shore, but they get tangled up in a rope hanging from the lifeboat. The three hop onto the boat and are taken on a wild dolphin-driven ride through the sea! Somehow they manage to get back to their boat, only to find that Dr. Ritter has taken up residence, then greets them before escorting them into Dr. Deep's lab. He continues to reveal the information about his plankton, such as the serious side-effect that comes with it: whenever it is ingested by a human, the human turns into a fish for life! He then forces Billy to choose one of the bottles of plankton and drink the contents. Billy attempts to distract him by turning around and messing with some pillows to give the impression of having turned into a fish. But Dr. Ritter forces him to drink the potion. Billy does, but he does not turn into a fish.
Dr. Ritter grows frustrated and a fight breaks out between the two scientists. Dr. Deep tries to hold Dr. Ritter down on the deck of the ship but he breaks free, grabs some plankton, and swallows it before Dr. Deep can call the police. Dr. Ritter then proceeds to transform into a fish and leaves, swimming away...
Sheena asks Billy why he did not turn into a fish, which he explains that he pretended to drink the plankton. Earlier, he managed to throw out the plankton from one of the bottles and then he replaced it with iced tea. Sheena begins to laugh because she apparently did the same thing! She planned to prank Billy in the same way. She then picks up another bottle and drinks the contents, though she is suddenly unsure if she picked the right one...
Deep Trouble II was adapted into a two-part episode of the Goosebumps TV series. It is the seventh (part one) and eight (part two) episode of season four, making it the final episode of the series. The episode is simply titled "Deep Trouble", omitting the "II".