After the gill-man escapes from Ocean Harbor Oceanarium in Florida, a team of scientists try to capture it in the Florida Everglades. The team is led by Doctor William Barton (Jeff Morrow), who is mentally unstable and an abusive husband to Marcia (Leigh Snowden). Seeing her with other men makes him jealous and paranoid. Unfortunately, the guide Jed Grant (Gregg Palmer) is inclined to flirt with her.
Marcia accompanies Jed and Doctor Tom Morgan (Rex Reason) on their first dive to search for the gill-man. She dives too deep and is overcome by Rapture of the Deep, which causes her to remove her SCUBA gear. She is saved by Jed and Tom, who temporarily abandon the search for their quarry.
Eventually, the Creature is captured, but it is badly burned by a fire, requiring a surgical transformation by Barton, Tom, Doctor Johnson (James Rawley), and Doctor Borg (Maurice Manson). The gill-man develops a rudimentary lung-system and begins to lose its gills. They dress it in clothes and try to teach it to live among humans, but it only wants to stare sadly at the ocean. In a murderous rage, Barton kills Jed and tries to blame the gill-man, who goes on a rampage. He rips down the electric fence, kills Barton, and returns to the sea.
The film was directed by John Sherwood when Jack Arnold, who had directed the first two Creature movies, graduated to classier pictures. It was based on a story by Arthur A. Ross, and the music was by Henry Mancini, who had scored the first film. On land, the creature was played by Don Megowan, and under water, once again by Ricou Browning. This is considered the last film in the Universal Classic Monsters series. It was filmed at Wakulla Springs, North Florida. Don Megowan was six-foot-nine, and it appears he was only dressed in clothes because he looked so good in them. Rex Reason and Jeff Morrow had starred in This Island Earth as Cal Meacham and the alien Exeter the year before. In the previous Creature films, the gill-man sank into the depths and was considered dead but came back. This time, however, when he returns to the sea, he is losing his gills and we do not know his fate.