Sewer Shark takes place in a post-apocalyptic future where environmental destruction has forced most of humanity to live underground. The player takes on the role of a rookie pilot in a band of "sewer jockeys", whose job is to exterminate dangerous mutated creatures to keep a vast network of sewers clean for "Solar City", an island paradise from which the evil Commissioner Stenchler (Robert Costanzo) gives his orders and critiques. The player's copilot, Ghost (David Underwood), evaluates the player's performance throughout the game, while a small robot named Catfish (voiced by Robert Weaver) scouts ahead and gives directions. The player is later assisted by Falco (Kari G. Peyton), a female jockey who believes that there is a hidden route to the surface. Falco is later captured by Stenchler, who threatens to mutate her into one of his mindless minions. This plot is thwarted when Ghost and the player reach Solar City.