During a battle in Antarctica with the original Gotengo, the monster Godzilla is entrapped under ice by a cave-in caused by a series of missiles fired off from the submarine. In later years, environmental disasters cause the appearance of giant monsters and superhumans, dubbed “mutants”, who are then recruited into the Earth Defense Force (EDF) to battle the monsters. An upgraded Gotengo, commanded by Captain Douglas Gordon, battles and destroys Manda in the English Channel off the coast of Normandy, but the ship is wrecked in the process and its captain is suspended from the EDF.

Mutant soldier Shinichi Ozaki is tasked with guarding a U.N. biologist, Dr. Miyuki Otonashi, who is sent to study a mummified monster. They are teleported to Infant Island where they encounter the Shobijin, fairies of Mothra, who reveal the mummified monster as Gigan, an alien cyborg sent to destroy the Earth who was ultimately defeated by Mothra. They warn that a battle between good and evil will happen soon and that Ozaki must choose a side. Suddenly, giant monsters attack several major cities: Rodan attacks New York City, Anguirus attacks Shanghai, Zilla attacks Sydney, King Caesar attacks Okinawa, Kamacuras attacks Paris, Kumonga attacks Phoenix, Ebirah attacks Tokai, and Hedorah attacks an unknown location. The EDF engages the creatures. The monsters mysteriously vanish at the same moment when an alien mothership appears over Tokyo. The aliens, named Xiliens, warn that an incoming planet called “Gorath” will soon impact the Earth. A peace pact is signed between Earth and the Xiliens. Meanwhile, Minilla, Godzilla’s son, is found in the forest by Kenta Taguchi and his grandfather Samon Taguchi.

Distrusting the Xiliens, Ozaki, Miyuki, and her sister, Anna discovers that the Gorath they saw is actually a hologram and that the aliens have replaced several members of the EDF with duplicates. After their kind is exposed, the Xiliens’ Controller, who called himself X during an interview on a radio show, kills his superior to assume command, revealing the plan to use humans as a food source while taking control of all the mutants except for Ozaki through a property in their DNA known as “M-base”. X also has the monsters placed under his control through M-base in their DNA and awakens Gigan to wipe out the EDF. The group escapes although Gigan pursues them. Gordon convinces them to travel to Antarctica to release Godzilla, which is immune to Xilien control thanks to his lack of M-base and easily destroys Gigan. The Gotengo then guides Godzilla into battle with the other monsters and returns to Tokyo to engage the Xiliens. After penetrating the mothership, the group is captured and brought before X as he summons Gorath to Earth. Though Godzilla destroys Gorath just before it crashes, it unleashes Monster X and the two monsters’ battle.

An upgraded Gigan joins Monster X but is intercepted by Mothra, who is gravely wounded while managing to destroy the cyborg. In the Xilien ship, X reveals that both he and Ozaki are superior beings known as “Keizers”, powerful beings distinct from regular mutants born on rare occasions when human DNA and M-base are combined, before directly taking control of Ozaki to turn him against the group. A fight breaks out, and X loses control of Ozaki due to the Shobijins’ blessing. X is fatally wounded, but he triggers the ship’s self-destruct as the group falls back to the Gotengo moments before the mothership explodes. Godzilla and Monster X continue their battle, but X transfers his Keizer energy to Monster X before dying, enabling Monster X to transform into its final form, Keizer Ghidorah. Godzilla is nearly killed by Keizer Ghidorah, but Ozaki manages to provide him with some of his own Keizer energy, giving him the strength to emerge victorious. Godzilla then shoots down the Gotengo, before turning his ire towards its crew after they leave the damaged vessel. Fortunately, Minilla shows up at the scene and convinces Godzilla not to kill the humans. The crew watch Godzilla and Minilla return to the ocean.