Having previously survived being riddled with bullets, the Gill-man is captured and sent to the Ocean Harbor Oceanarium in Florida, where he is studied by animal psychologist Professor Clete Ferguson and ichthyology student Helen Dobson.

Helen and Clete quickly begin to fall in love, much to the chagrin of Joe Hayes, the Gill-man's keeper.

Unable to stop thinking about Helen, the Gill-man soon begins to stalk her and Clete, ultimately abducting her from a seaside restaurant where the two are at a party.

[5] Revenge of the Creature marks the screen debut of Clint Eastwood, who appears uncredited as a lab technician named Jennings early in the story.

Other than some interesting sequences involving the setting, "what is probably the most unusual aquarium in the world makes a nice, picturesque background indeed ..." the review was dismissive of the production.

[7][8] Writing for AllMovie, author Hal Erickson reported that although the film is "[n]ot nearly as good as the first Creature [from the Black Lagoon], this followup is saved by the underwater photography".

[11] In 1997, Revenge of the Creature was mocked on the comedy television series Mystery Science Theater 3000, marking its first episode on the Sci-Fi Channel.