A team of local scientists discover an invasion by intelligent parasitic creatures from deep beneath the Earth while investigating a mysterious, five-story-tall, metallic cone-shaped object which has suddenly appeared outside the small town of Riverdale, Illinois. It quickly becomes obvious that the creatures' first victims, whose minds have been taken over, are the town's leading citizens.
In Riverdale, Illinois, a man (Hampton Fancher, uncredited) is shown carrying a lighted, basketball-sized glass container bumps into a pedestrian, and the container is broken. A fight ensues and a hissing sound is heard.
Glenn Cameron (Factor) and his fiancée, Elaine Cameron (Jody Fair), are driving by when they are distracted by a bright light from the nearby woods. They stop to investigate and find three dead animals, and to their surprise, they come upon a large, cone-shaped, spiral metal structure resembling the tip of a screw.
Two days later in Washington, D.C., a flying saucer investigation committee reviews classified army footage of the object. Sen. Walter K. Powers (Cornelius Keefe) and his assistant Dan Walker (Robert Ball) arrive late for the briefing, which notes that the metal object stands 50 feet high with a base diameter of 50 feet. The nature and origin of this spiral metal cone is unknown. Dr. Paul Kettering (Ed Nelson) is the chief investigator. Also noted is the murder of several people in the nearby town. The senator and his assistant fly to Riverdale to investigate. They are met by Glenn Cameron, who explains that his father, the mayor, is missing. The three drive to the metal object's location. Alice Summers (Lee), the mayor's secretary, assists Kettering by recording test results. The senator climbs scaffolding erected around the spiral cone to question Kettering and his assistant, Dr. Wyler (David Hughes). Kettering explains that it appears to be indestructible, then crawls inside to explore. Some time later, Wyler prepares to go inside, just as Kettering crawls out; the interior is made up of a maze of small, winding tunnels. A call to their field phone informs them that the mayor has returned to his office.
Mayor Cameron (Orville Sherman) acts as if possessed. Taking a pistol from his desk drawer, he struggles to point it at his head. Kettering, the senator, Alice and Glenn arrive at town hall. The mayor is hostile and angry, even towards his son. Kettering notices an odd mound near the mayor's neck, under his suit coat. The mayor pulls the pistol on the group. Kettering asks him about the mound, and the mayor strikes his son while attempting to flee the room. As he does, Kettering hits the mayor, who discharges several gunshots. The mayor is shot and killed in the hallway by a deputy.
An autopsy reveals something strange. The doctor (Doug Banks) and Kettering find a dead creature of unknown origin attached to the mayor's neck; it injected some kind of toxin into his nervous system. Even without being shot to death, he would have died within 24–48 hours.
As the sheriff (Greigh Phillips) drives toward the metal object, he encounters a man lying on the road, and is attacked by the man as he gets out of his patrol car. Nearby, another man, holding a lighted glass container, watches the fight. The sheriff is knocked out, and the two men remove something from the container. The sheriff revives, and the three drive off in the patrol car.
While working with Alice in the lab, Kettering experiments with a piece of the creature taken from the mayor's body. It attaches itself to his arm just like a parasite, but he is able to free himself by burning it with a Bunsen burner. Wyler calls Kettering at the lab, and they drive out to the metal cone. Along the way, they discover an abandoned electric company utility truck. A call to the sheriff from Sen. Powers goes unanswered, as the sheriff struggles with being possessed. Three groups are organized to search for other strange metal objects. Kettering and Alice find the dead body of the utility truck's driver with two puncture wounds on the back of his neck. While searching, Glenn and Elaine are locked inside an empty cabin. Someone tries to set the cabin on fire, but Glenn shoots at the arsonist, and he and his fiancée are able to escape. The three groups later reassemble at the mayor's office. There, they discover two glowing containers containing more parasites. The senator calls the telegraph office to send a warning to the governor. The telegrapher (Henry Randolph) takes down the message, but being possessed, does not send it.
Three men drive to Alice's apartment building and plant a parasite in her room. She is possessed and joins the three men in their car. Paul and Glenn later discover she is missing. They drive back to the spiral cone and discover a dying man they recognize as Prof. Helsingman (Saul Bronson), who vanished five years earlier along with a scientific expedition team. They discover marks on his neck and take him to a hospital. Kettering questions the professor, but he only utters the word "Carboniferous", referring to a geologic time period millions of years ago. Sen. Powers tries to make several telephone calls, but is consistently told that the lines are busy. Glenn and Paul go to the telegraph office to find out if the warning was sent to the governor's office. They are attacked but manage to subdue their assailants and flee.
Kettering climbs the metal object's scaffolding to check on his equipment. He realizes the two deputies on guard are now possessed, and both are shot and killed. Kettering and Glenn crawl inside the spiral metal cone and discover, behind a sliding tunnel wall, a room filled with a heavy mist. They are greeted by another member of the missing expedition, an old, bearded man (Nimoy). He tells Kettering he was once Prof. Cole and explains, "Now I hold a position of a much higher order". He provides details about the parasites' invasion, which is coming from inside the Earth, and says, "We shall force upon Man a life free from strife and turmoil. Ironic that Man should obtain his long sought utopia as a gift, rather than as something earned". After the possessed Cole disappears, Kettering shoots and kills the lurking sheriff. Parasites on the loose chase Kettering and Glenn outside.
Kettering formulates a plan using the abandoned power company truck. He connects an electrical wire from one end of the ravine to the other using a harpoon gun. He prepares to shoot a connecting wire from the metal object to an overhead high voltage transmission line, completing a circuit. Before Kettering can finish, Alice exits the spiral cone and appears on the scaffolding. Kettering climbs up to rescue her, but being possessed, she refuses to come with him. She pulls a pistol and shoots him, and he falls to his death. Glenn fires the harpoon gun, making the connection to the overhead transmission lines, which engulfs the grounded metal cone in high-voltage sparks. Alice collapses as the parasites inside the object are electrocuted. Sen. Powers and Glenn crawl inside and verify that the menace has been eliminated. Later, as Glenn and Elaine walk away from the site, they embrace.
Actor VeSota wanted to direct, so he approached Corman with the script. Corman helped him raise the modest financing needed, as well as arranging distribution through AIP. The film was shot over six days on a budget of $26,000.
The Brain Eaters was known during production as, variously, The Keepers, The Keepers of the Earth, Attack of the Blood Leeches and Battle of the Brain Eaters.
After its release, science fiction author Robert A. Heinlein sued for plagiarism, asking for damages of $150,000, claiming that The Brain Eaters was based on his novel The Puppet Masters. Corman insisted that he was unfamiliar with Heinlein's work, both while reading the script and during the film's production. He did, however, see the obvious references once he read the novel, so he settled out of court for $5,000. Heinlein also demanded that he receive no screen credit, as he found the film "wanting". This lawsuit halted actor John Payne's intention of producing a film based on Heinlein's novel.
Posters for The Brain Eaters appeared in the movie theater scenes in the film System Shock 2.