Two hunters seek refuge from raging thunderstorm at the Willows House, which is supposedly abandoned and haunted. They find it to be occupied by Dr. Eric Vornoff, who repeatedly denies them hospitality. One of the hunters attempts to use his rifle to force his entry into the house, but the menacing giant Lobo appears and scares them away.
From a secret laboratory within Willows House, Vornoff releases a giant octopus from its tank and sends it after the intruders. It kills one of them, while the other is captured by Lobo to become an unwilling test subject in an experiment that will either give the captive the strength of twenty men, or kill him. The man dies on the operating table and Vornoff is disheartened.
In a police station, Officer Kelton asks to work the case of the monster of Lake Marsh. His superior Captain Tom Robbins of the Homicide department turns him down and instead asks to see Lieutenant Dick Craig. Robbins and Craig discus the 12 missing victims. Newspaper reporter Janet Lawton arrives and forces her way into Robbins' office. Janet states her intention to go to Lake Marsh personally to investigate the place and leaves the station, despite her fiancee Lt. Craig's protests.
Janet engages in some research at her newspaper's archives while Robbins and Craig meet with an intellectual from Europe, Professor Vladimir Strowski. He claims that there are significant similarities between the case of the Monster of Lake Marsh and that of the Loch Ness Monster. He seemingly agrees to assist the police in investigating the Marsh, but not at night, which puzzles Robbins.
As night falls and another storm begins, Janet drives alone to Lake Marsh. She wrecks her car and is immediately threatened by a large snake. As she passes out from fear, Lobo wrestles with the snake to rescue her. Later, Janet wakes up to find herself a prisoner of Vornoff, who uses hypnosis to put her back to sleep.
The following day, Craig and his partner drive to the area around Lake Marsh, though Strowski missed his scheduled appointment with the police. They discover Janet's abandoned car and realize she is now the 13th missing victim.
At the Willows House, Janet wakes up and takes in her strange surroundings. Vornoff and Lobo are there to greet her and offer tea. Vornoff assures her that Lobo is harmless, but the giant seems fascinated with her and approaches the female captive with questionable intent. Vornoff beats Lobo to drive him away. Vornoff explains that he found Lobo in Tibet, then abruptly ends the conversation by hypnotically placing Janet back to sleep. He orders Lobo to transport Janet to Vornoff's private quarters
Strowski arrives at Willows House and Vornoff greets him. They are revealed to be old acquaintances. Strowski explains that he has spent years tracking down Vornoff. They have had several near-encounters, in Paris, London, and at Loch Ness. Their (unspecified) country of origin is interested in the exiled scientist's groundbreaking experiments with atomic energy and wants to recruit him. Vornoff rebukes Strowski, revealing that he feels no loyalty to the country and scorned him.
Strowski pulls a gun on his old colleague, and Lobo arrives to defend his master. Lobo defeats Strowski, whom Vornoff then feeds to his octopus.
That evening, Craig and his partner return to the swamp and discover Strowski's abandoned car. They split up and Craig heads towards Willows House. In the secret laboratory, Vornoff telepathically summons Janet to his current location. She arrives dressed as a bride. Vornoff has decided to use her as the next subject of his experiments. Lobo is reluctant to take part in this experiment, and Vornoff uses a whip to re-assert his control over his slave and assistant. Craig enters the house and accidentally discovers the secret passage. He is captured by Vornoff and Lobo.
As the experiment is about to begin, Lobo is distressed. He is torn between his loyalty to Vornoff and his infatuation with Janet. Lobo rebels and attacks his master. Vornoff shoots at his servant, but the bullets have no effect. Lobo knocks him out, frees Janet, and places the unconscious Vornoff on the operating table. The scientist then becomes the subject of his own human experiment.
Janet releases Craig, who attempts to stop Lobo. Craig is once again defeated and knocked out. The experiment is successful and Vornoff is transformed to an superhuman being. He and Lobo physically struggle with each other, and Vornoff defeats Lobo. Their fight destroys the laboratory and starts a fire. Vornoff grabs Janet and escapes from the flames.
Captain Robbins and other police officers arrive to help Craig. The police pursue Vornoff through the woods. A lightning strike then destroys Willows House. With his home and equipment ruined, a distressed Vornoff abandons Janet and attempts to escape. Craig rolls a boulder at him and Vornoff is knocked into the water with the octopus. A nuclear chain reaction started at the destroyed laboratory kills Vornoff and the octopus. The film ends with Robbins commenting that Vornoff "tampered in God's domain".
- Bela Lugosi - Dr. Erik Vornoff
- Tor Johnson - Lobo
- Loretta King - Janet Lawton
- Tony McCoy - Lt. Dick Craig
- Harvey B. Dunn - Captain Robbins
- Paul Marco - Officer Kelton
- George Becwar - Professor Strowski
- Ann Willner - Tillie
- Dolores Fuller - Margie
- Ben Frommer - Drunk
- Production of this film was dramatized in the 1994 feature film Ed Wood.
- There are rumors that Ed Wood and his crew stole the rubber octopus from Republic Studios (as dramatized in the film Ed Wood). However, records exist showing the octopus was legally rented, along with some cars, though Wood and his crew either forgot to take the motor for the octopus' tentacles or none of the crew knew how to operate it. Because of this, whenever a character was attacked by the octopus, the victim had to pull the tentacles around himself, and writhe and struggle to make it seem as though he were actually being attacked.
- Bela Lugosi was paid $1,000 for his appearance in this film, which is roughly the equivalent of $10,000 in 2021, adjusted for inflation.
- Ed Wood wrote this film with his then-girlfriend Dolores Fuller in mind as the lead. However, the part was given to Loretta King and Delores was recast as a secretary. Money soon ran out and production was temporarily halted. The film Ed Wood depicts Ed Wood as believing that King would finance the movie herself; this mostly comes from a story told by Fuller, and King always denied that she made any promise for any more funding than what she actually gave. (Ed Wood depicts this confusion ambiguously, thus avoiding any inadvertent slander.) Wood then found a young actor named Tony McCoy whose father was wealthy, and Mr. McCoy agreed to finance the film under the conditions that his son Tony play the lead—and that the movie end with a nuclear explosion.
- A sequel (of sorts) to Bride of the Monster was made in 1959. Entitled Night of the Ghouls, the film went undeveloped in a photo lab for over 20 years, as Wood couldn't afford the processing fees. The film was finally released in 1987 and is available on home video. These two films along with Plan 9 from Outer Space form the "Kelton Trilogy", named after the character Officer Kelton (played by Paul Marco) who appeared in all three films. Tor Johnson also reprised the role of Lobo.
- Was nominated in The Golden Turkey Awards series for Least Convincing Scientific Explanation in Motion Picture History. It "lost" to The Bride and the Beast (which Wood co-wrote).