Dr. Robert Bolton had invented a gene-slamming device for peaceful uses until his colleague Dr. Luther Paradigm uses it for his evil purposes. When Dr. Bolton tries to intervene, he ends up gene-slammed into an unseen inhuman creature during the struggle and escapes. While in search of their father, John, Clint, Robert, and Coop are mutated into humanoid sharks by the evil Dr. Paradigm. While adapting to their new looks, the four brothers must avoid being seen.

The Street Sharks are on a runaway from the police along with their friends Bends and Dr. Lena. The Street Sharks must find a new place to live in and be safe from society.

Ripster, Jab, Streex, and Slammu must protect their reputations and change the way they are being viewed in Fission City. They must fight Dr. Piranoid as well as finding their father once and for all.

Dr. Paradigm captures Big Slammu to control his mind and the Street Sharks must break into Dr. Paradigm's hideout to save their brother.

While the Street Sharks are going out for burgers, Dr. Paradigm transforms a squid he has acquired into Killamari who becomes the latest member of the Seaviates. The Sharks have to stop them from breaking into the Bolton home and stealing important genetic research data that their father left behind.

When a musician called Melvin Kresnik accidentally digests contaminated popcorn and water that was tainted with a gene-slamming chemical, he becomes a mako shark later known as Rox and befriends the Street Sharks. Together, they have to save the concert in town and its attendants from being mutated into more sea creatures through the same way that Rox was mutated.

The citizens of Fission City hear an announcement from Dr. Paradigm that he has invented a vaccine against the gene-slamming formula.

With the help of a mind-control serum, Dr. Paradigm turns Jets Taylor into a killer whale mutant named Moby Lick to be his latest Seaviate.

When Streex has been captured by Dr. Paradigm, the rest of the Street Sharks alongside Moby Lick take to the roads to rescue him.

Rox is back in town for the Fission City Music Awards and plans to play the evidence that would expose Dr. Paradigm's gene-slamming activities.

When his hotel had been previously destroyed by the Street Sharks and no family members to live with, Mr. Cunneyworth allows Dr. Paradigm to gene-slam him with the DNA of an electric eel and a moray eel which transforms him into Repteel. While Repteel is ordered by Dr. Paradigm to steal an advanced supercomputer part for his robotic machine, the Street Sharks take a cruise around the city to find the doctor's new Seaviate's location and put a stop to their evil plans.

The Street Sharks are framed and brought out of hiding by Sharkbot, the robotic machine built by Dr. Paradigm in the last episode. The Street Sharks must once again defend their reputations and take on Sharkbot.

The Street Sharks discover an underground civilization of mutant crocodiles that happen to know Dr. Bolton after he cured them of their damaged genes. Meanwhile, Dr. Paradigm rebuilds Sharkbot and captures one of the mutant crocodiles.