The film opens with a fishing boat being attacked by a giant octopus out at sea during a storm. The octopus is soon attacked by a green gargantuan creature, who, after defeating the octopus, attacks the boat and eats all but one of its crew. The surviving crew member is found and later wakes up in a hospital telling the authorities of his encounter with the gargantua, but no one believes him. Days afterward, people begin disappearing out at sea, and soon, the very same gargantua is seen by a group of villagers when they try pulling in a net of fish.
The gargantua attacks begin to increase, and soon, on a cloudy day, the green giant makes landfall at Haneda Airport, snatching a poor woman from her office and devouring her alive. The monster retreats back to the ocean when it becomes too bright outside for him. Called in from the U.N. are Dr. Paul Stewart (Russ Tamblyn), and his assistant, Akemi (Kumi Mizuno). The pair discuss how the gargantua may be related to another Frankenstein creature that they had encountered once before, whom they had named Sanda. However, Sanda was a kind and gentle creature, and when he left the laboratory, he even told Akemi goodbye. Stewart and Akemi are reluctant to believe that Sanda could have become such a murderous beast.
The gargantua attacks again, and the JSDF soon retaliates, and when the monster appears again, inland and away from sea, the military unleashes its newest weapon: the Maser Cannon. Eventually, Gaira, as he is called, is lured into a trap where the military set up electrodes in a nearby river which, in conjunction with the masers, almost kill him. Before Gaira can be finished, Sanda appears and fends off the JSDF, without once harming a single person. After saving his kin, Sanda attempts to help Gaira heal his wounds. Meanwhile, Stewart and Akemi, both relieved that Sanda is alive and not the monster that's been attacking people, go to the forests near the location of Sanda's reappearance, believing the area to be safe from Gaira as long as it is daylight outside.
While exploring the countryside, Stewart hypothesizes that Gaira could have been the result of a piece of Sanda's flesh that had fallen off at some point, making Gaira more of a clone than a brother. However, Gaira has begun healing, and he soon attacks a group of hikers in the forest and on the mountain, Akemi and Stewart among them. While trying to escape, Akemi is injured and almost falls off a cliff into a lake below, but she is saved by Sanda, who suffers a leg injury as a result of his heroics. Akemi realizes that Sanda remembers her. After returning to check up on his "brother", Sanda sees human remains lying around Gaira, who is sleeping off his most recent meal. Angered at this, Sanda attacks Gaira, who retaliates before fleeing into the countryside.
Eventually, Gaira ends up in Tokyo. To fend off the beast, every light in the city is turned on, but Dr. Stewart realizes that Gaira has come to associate light with food, and tells the military to have everyone shut off their lights. Gaira terrorizes the city until Sanda arrives. Sanda desperately pleads with Gaira to stop his bloodthirsty ways, but the green gargantua is too bloodthirsty and violent to consider such a notion, and attacks his brother before the military steps in to give Sanda a chance. The two gargantuas then engage in an epic struggle to the death, destroying a significant portion of the city in the process before they finally take their fight the ocean. Eventually, the two gargantuas are swallowed by a volcano and the film ends.