The Allies move closer toward defeating Nazi Germany. In a castle laboratory near the front lines, Dr. Reisendorf studies a mysterious object. German troops arrive, showing Dr. Reisendorf orders to remove the object. Despite his protests, the object is taken away, lowered into a U-boat. The U-boat undertakes the perilous voyage from Germany to the Indian Ocean. It rendezvous with a Japanese sub. The object is taken from the U-boat to the Japanese sub. Just then, a US seaplane spots the rendezvous. Bombs destroy the U-boat while the Japanese sub dives and makes its escape.
Within the Japanese sub, Lt. Kawai wonders what is within the trunk, what the Nazis would risk an entire U-boat to get to Japan. He is given the chance to find out when he delivers the trunk to a research facility in Hiroshima. It is the heart of Frankenstein's monster. Still living, still beating. It can never die. The Japanese hope to learn how to grow any part of the human body by studying the thing. Such research is ended months later when the A-bomb is dropped on Hiroshima.
Years later, Dr. James Bowen works at a hospital near Hiroshima devoted to treating the victims of the atomic bomb. Often terminal, the patients are a melancholy sight. Dr. Bowen's colleagues in research are Dr. Sueko Togami and Dr. Kenichiro Kawaji. Bowen regrets that their research has not advanced to a point at which they can save lives. Bowen hopes that science can learn much from this tragedy, and so some good can come from the suffering.
Returning home, Dr. Togami encounters a man chasing a strange boy who has stolen his dog, intending to eat it. The boy escapes. Local schoolchildren are horrified to see a butchered and partially eaten rabbit strewn about their classroom.
Dr. Bowen and Sueko are about to eat dinner together when there is a commotion outside. Down below, they see a motorist flee the scene of an accident. The thing he struck is the strange boy. Sueko tosses a packet of meat down to the creature. The boy limps over and takes the food, scuttling off into the rainy night.
The next day, on the beach, Bowen and Togami encounter a mob of villagers. They are pursuing the strange boy, who has hidden within one of the cliff-side caves. Bowen and Sueko join the pursuit and manage to subdue the boy. It is decided to take the creature to the institute. The press marvels over the strange boy, who remains mute. Kawaji and Bowen insist the boy is Caucasian and has received large amounts of radiation. More importantly, he has not succumbed to the radioactivity. Instead, he is building up resistance to it. Bowen requests help finding out who the boy's parents are and where he grew up.
Elsewhere, at an offshore oil-drilling site, former Lieutenant Kawai recollects about the Frankenstein heart after reading about the boy in Hiroshima. An earthquake strikes the area, causing massive damage. As oil shoots into the air, a great fissure opens up. Kawai has a brief glimpse of some monstrous thing within the crevice before the culprit retreats back into the depths.
Back at the institute, the creature is mesmerized by TV, even though he doesn't react to words. Agitated, he attacks the TV. Sueko calms him down, but the monster becomes fascinated by her necklace, taking it from her, not even noticing when Bowen breaks a chair over his back. Laughing like a child, the man-sized creature allows himself to be lead away.
Sueko and Bowen discuss the monster's rapid growth rate, wondering if it might be due to radioactivity. Dr. Kawaji has received hundreds of letters, but none seem to help. The monster has grown so large, that he is now confined to a cell and kept chained. The hospital is becoming anxious to get rid of the monster, the director suggesting that he be removed to a zoo.
Kawai arrives and discusses his memories of the Frankenstein heart with Bowen, Togami and Kawaji. This information is both horrifying and illuminating. Bowen suggests trying to find any of the people who knew about the heart back in WWII. Dr. Kawaji goes to Frankfurt and meets with Dr. Reisendorf. Dr. Reisendorf tells Kawaji that the only way to find out if the creature is Frankenstein, it would be necessary to cut off an arm or leg. If the creature is Frankenstein, the limbs will grow again and the severed limbs will also remain alive.
Dr. Kawaji returns, telling Bowen and Sueko about what he has learned. The other scientists are opposed to Dr. Kawaji's plan to cut off a leg or arm to test and see if the creature is Frankenstein. Bowen and Sueko leave the hospital, expecting Kawaji to join them for dinner. They do not know that Dr. Kawaji is actually back at the institute, preparing to conduct this test. The untimely arrival of reporters interrupts him. The monster reacts angrily and rips his way out of the cell and the chain. Now over twenty feet tall, the monster is free. Dr. Bowen hurries to the hospital, leaving Sueko behind. Bowen organizes an attempt to contain the monster, but police fire on him, causing the monster to break out the hospital wall and flee into the city.
Sueko listens to the news on the radio. The giant appears outside her apartment, as if to say goodbye. The Frankenstein giant flees from police, managing to beat off a squad car with a lamppost. The giant makes his escape into the countryside.
At a press conference, Bowen and Kawaji express hopes that the monster will not be killed. Reporters examine the chain and the cell, thinking the monster may have escaped through negligence. They have just reached the conclusion that the chain was too large when they see Frankenstein's severed hand crawling away. The scientists soon arrive and Dr. Kawaji captures the living hand. He places it in a protein solution to keep it alive. Dr. Togami hopes that the monster can be captured, but the police are concerned about what they can do with him if he is caught. Reports come in that Frankenstein has been seen in Okayama. The city is at once placed under alert. Despite the best efforts, the monster is eluding police.
In the lab, Dr. Kawaji's hopes of keeping the hand alive are realized. Meanwhile, the monster appears in Himeji, devouring cattle. Kawaji and Bowen meet with Okayama police, trying to determine a plan of defense. The monster is lingering in the Osaka area.
A ship of partying students receives a terrifying surprise when Frankenstein appears in the bay. The giant stops the ship with his partially reformed hand, but does not try to sink it, quickly submerging again.
Back in Hiroshima, the hand is gone. Dr. Kawaji soon finds it. The hand is now dead, but it had grown to an enormous size before it escaped and died.
A village near Mt. Ibuki is the next site of Frankenstein's appearance. It does not take long for the JSDF to be notified. Tanks enter the forest to attack the giant, only to fall prey to the pit traps the monster lures them into. Taunting the frustrated tank crews, the giant disappears back into the forest.
In Hiroshima, Dr. Bowen realizes that the giant is seeking out a climate similar to the cold climate of Germany. He leaves the heights of the mountains to find food. Bowen is convinced that the monster must be given food and induced to settle in one place, where he can be studied. He predicts that the monster will next be seen on the slopes of Mt. Fuji.
A small skiing village in the mountains is populated by partying students. The party is over, however, when the mountainside crumbles away and the burrowing monster Baragon emerges. Roaring, the voracious beast attacks, devouring everyone, leaving no witnesses to his attack.
The next day, the JSDF and the scientists examine the destruction. The army decides that the reason there are no bodies is that Frankenstein ate them all. The scientists hold a press conference. Bowen and Kawaji are convinced that Frankenstein is not responsible, though the press remains unconvinced.
A mining operation breaks into a natural cavern following a tunnel disaster. They catch a brief glimpse of Baragon's glowing horn, but cannot decide what they have seen.
From helicopter, the scientists try to find Frankenstein before the military can. Meanwhile, Baragon attacks an isolated farm, devouring everything, human and otherwise. Returning from school, the children discover Frankenstein lurking within a nearby cavern. JSDF troops arrive with the scientists. They soon find the monster, but their bullets only anger him. The monster drives his attackers off and emerges from the cave, fleeing into the wilderness. After this, even the scientists are convinced Frankenstein is guilty. Mr. Kawai returns, telling them about the disaster at the oil field, and the other monster that he saw. He is convinced that this other monster is responsible for the attacks and recent tunnel disasters. Kawai takes his story to the press, but nobody believes him. Similarly, the rest of the scientific community laughs at his theory of dinosaurs retreating below ground to remain warm and surviving into the present as unseen, burrowing beasts. Disheartened, Kawai departs, promising to return as soon as he can afford it. Kawai is not the only one running out of money. Bowen, Sueko and Kawaji have only enough money for one last search with the helicopter.
That day, the search reveals that the food they left has been taken. They leave more and soon, the now fifty-foot Frankenstein emerges from his cave and takes the food back into his home.
The scientists decide to go in on foot to try and help Frankenstein. Hiking into the forest, Bowen discovers that Kawaji has no interest in saving Frankenstein, when he finds that Kawaji is carrying chemical bombs to blind Frankenstein with. Kawaji says that the JSDF is sure to kill the giant, at least his way the body will be intact and he will be able to study the monster's heart and brain. Kawaji demonstrates one of his bombs for his colleagues. The explosion attracts Baragon. Bowen and Kawaji hurl the bombs at the awful dinosaur beast, but with no effect. Fleeing from Baragon, Dr. Togami falls. Before she can be eaten, Frankenstein arrives, intercepting Baragon and wrestling with the brute. Bowen helps Sueko to safety as the two monsters fight. Baragon tries to use his fiery breath and powerful leaping ability to fend off the giant. Lost, Dr. Kawaji is knocked out by rocks kicked up by the monsters.
With Baragon burrowing back underground, Frankenstein finds Dr. Kawaji. He picks up the scientist. As Bowen and Sueko drive away, Frankenstein steps into the road and hands them the wounded Kawaji. He quickly leaves; Baragon is still nearby, preparing to attack a village. Frankenstein blocks the monster's path and the battle begins anew. The village evacuates while Frankenstein holds off Baragon.
The battle is ferocious. Frankenstein hurls boulders at Baragon while Baragon lashes out with his fiery breath. Chasing Frankenstein, the battle soon reaches Frankenstein's cave lair. Trying to fend off Baragon with burning logs, the giant only succeeds in setting the forest on fire. Enraged, the two monsters fight as the woods burn around them. Baragon again burrows underground, but soon reemerges, determined to have Frankenstein's blood. It is an unwise decision, for after a tremendous struggle, the Frankenstein giant manages to grasp Baragon's head. Straining, Frankenstein is at last able to break Baragon's neck. He does not have time to savor his victory. As Dr. Bowen, Sueko and Kawaji watch, the battlefield is surrounded by flames. Worse, the already weakened ground gives way. Both the triumphant Frankenstein and Baragon's body sink from sight into the earth.
Dr. Kawaji points out, however, that Frankenstein can never truly die and that one day they will hear of him again.