Elisa is a mute, isolated woman who works as a cleaning lady in a hidden, high-security government laboratory in 1962 Baltimore. Her life changes forever when she discovers the lab’s classified secret — a mysterious, scaled creature from South America that lives in a water tank. As Elisa develops a unique bond with her new friend, she soon learns that its fate and very survival lies in the hands of a hostile government agent and a marine biologist.
Elisa Esposito, found in a river as an orphaned child with wounds on her neck, is mute and communicates through sign language. In 1962, Elisa lives alone in an apartment above a cinema. She works as a cleaning woman at a secret government laboratory in Baltimore at the height of the Cold War. Her only friends are her next-door neighbor Giles, a struggling gay advertising illustrator who shares a strong bond with her, and her co-worker Zelda, an African-American woman who also serves as her interpreter at work.
The facility receives a tank with a mysterious creature captured from a South American river by Colonel Richard Strickland. Curious, Elisa discovers that the creature is a humanoid amphibian and begins visiting him in secret, forming a close bond with him.
Seeking to exploit the creature for possible advantages in the Space Race, General Frank Hoyt orders Strickland to vivisect it. One scientist, Dr. Robert Hoffstetler, who is secretly a Soviet spy named Dimitri Mosenkov, pleads unsuccessfully to keep the creature alive for further study and, at the same time, is ordered by his Soviet spymasters to euthanize the creature. Elisa learns what the Americans’ plan is for the creature, and she persuades Giles to help free him. Mosenkov discovers Elisa’s plot and chooses to help her. Though initially opposed to the plan, Zelda becomes involved as the escape becomes successful.
Elisa keeps the creature in her bathtub, adding large amounts of special salts to the water, planning to release him into a nearby canal when it opens to the ocean in several days. As part of his efforts to recover the creature, Strickland interrogates Elisa and Zelda, but the failure of his advances toward Elisa hampers his judgment, and he dismisses them. Back at the apartment, Giles discovers the creature eating one of his cats. Startled, the creature slashes Giles’s arm and bolts from the apartment. The creature gets as far as the cinema downstairs before Elisa finds him and returns him to her apartment. The creature touches Giles on his balding head and his wounded arm, and the next morning, Giles discovers that his hair has partly grown back and the wounds on his arm are healed. Elisa and the creature soon become romantically involved, having sex in her bathroom, which she at one point floods for him.
Hoyt gives Strickland an ultimatum to recover the creature within 36 hours. Meanwhile, Mosenkov is told by his handlers that he will be extracted in two days. As the planned release date approaches, the creature’s health starts deteriorating. Mosenkov leaves to rendezvous with his handlers, with Strickland tailing him. At the rendezvous, Mosenkov is shot by one of his handlers, but Strickland shoots the handlers dead and then tortures Mosenkov for information. Mosenkov implicates Elisa and Zelda before he dies from his wounds. Strickland then threatens Zelda in her home, causing her terrified husband to reveal that Elisa had been keeping the creature. Strickland searches Elisa’s apartment and finds a calendar note revealing where she is taking the creature.
At the canal, Elisa and Giles bid farewell to the creature, but Strickland arrives and attacks them all. Strickland knocks Giles down and shoots the creature and Elisa, who both appear to die. However, the creature heals himself and slashes Strickland’s throat. As police arrive on the scene with Zelda, the creature takes Elisa and jumps into the canal, where deep under water he heals her. When he applies his healing touch to the scars on her neck, she starts to breathe through gills. In a closing narration, Giles expresses his belief that Elisa lived “happily ever after” with the creature.