Set in the not-too-distant future, humanity has been forced to live in their underground infrastructures for unspecified reasons. Here, bands of "Sewer Jockies" group together and with the use of their armed ships, scour the tunnel systems in order to exterminate the mutated creatures that inhabit the sewers to prevent them from contaminating the above-ground resort area of Solar City.
The player assumes the role of a rookie pilot and is joined by a veteran pilot, Ghost, who proceeds to berate the player for the majority of the game, and his robot scout, Catfish, who provides the player with valuable information. Throughout the game, the player receives transmissions from the owner of Solar City, Commissioner Stenchler, who will allow the player into his resort should they kill one million pounds worth of creatures.
Meanwhile, a fellow jockey by the name of Falco rides into unsanctioned territory following what she describes as a "crazy looking thing," thinking it will lead her on a secret path to Solar City. Later, this creature provides the route for players as opposed to receiving this information from Catfish.
As a rail shooter, the player does not take direct control of the ship, but that of the targeting crosshair in order to shoot the various species as they appear. The player does, however, have limited control of the ship during specific navigation spots. While the directions are always different, there is only one specific route to through the sewer for each time the game is played, as specified by Catfish. Occasionally, Catfish will give the player a series of directions (3, 6, 9 or 12) which must be followed or the game will end. When approaching one of the navigation spots, the player must hold down the A button and press the appropriate direction.
While originally released on the Sega CD, Sewer Shark was first conceived to be the flagship product of Hasbro and Nolan Bushnell's ill-fated Control-Vision video game console (also referred to as NEMO), which used VHS tapes as opposed to compact discs. The NEMO was eventually canceled and Digital Pictures picked Sewer Shark up for production along with Night Trap.