The crypto-zoological agency Monarch faces off against a battery of god-sized monsters, including the mighty Godzilla, who collides with Mothra, Rodan, and his ultimate nemesis, the three-headed King Ghidorah.

The new story follows the heroic efforts of the crypto-zoological agency Monarch as its members face off against a battery of god sized monsters, including the mighty Godzilla, who collides with Mothra, Rodan, and his ultimate nemesis, the three headed King Ghidorah. When these ancient superspecies, thought to be mere myths, rise again, they all vie for supremacy, leaving humanity's very existence hanging in the balance.

As the world is still recovering from the fact that monsters exist, they face a new threat: the return of the Titans. Now the crypto-zoological agency Monarch has only one chance to stop them: let Godzilla fight it out as the whole world itself will tremble as it watches Mothra, Rodan, Ghidorah, and Godzilla fight for the title King of the Monsters

Five quiet years after the first sighting of the MUTOs and the catastrophic events that nearly levelled San Francisco in Godzilla (2014), Dr Emma Russell's powerful bio-acoustics generator, the Orca, triggers a worldwide awakening of the Hollow Earth's Titans. As the ancient long-dormant giants resurface one by one, the radical eco-terrorist, Colonel Alan Jonah, gets his hands on the audio device, hell-bent on restoring nature's balance; however, what started as a dangerous but logical theory, now threatens to obliterate the entire human species. As a result, the ultimate Kaiju and King of Monsters, Godzilla, has to do battle with an omnipotent lightning-spitting challenger for the title: the three-headed Monster Zero, Ghidorah. Is Godzilla humankind's defender or its enemy?—Nick Riganas

Dr. Emma Russell (Vera Farmiga) is a Paleobiologist for the Crypto-zoological organization Monarch, which seeks out and studies giant creatures known as "Titans". She and her daughter Madison (Millie Bobby Brown) witness the birth of a giant larva dubbed Mothra inside the Monarch base (disguised as a Mayan Pyramid). Emma calms Mothra down with the "Orca", a device capable of emitting frequencies that can attract or alter Titan behavior. A group of ecological-terrorists, led by Alan Jonah (Charles Dance), suddenly attack the base and kidnaps Emma and Madison.

Mothra flees and pupates under a waterfall. Monarch scientists Dr. Ishiro Serizawa (Ken Watanabe) and Dr. Vivienne Graham (Sally Hawkins) approach Mark Russell (Kyle Chandler), Emma's ex-husband and Madison's father, to track them down. They tell him that the Monarch team is tracking 17 monsters. Mark wants them destroyed but Serizawa believes some of them are benevolent. Serizawa wants Mark's help to decode the frequencies Emma combined in the Orca, so that they can track the Orca and hence track Emma and Madison. Mark speculates that Alan is using Mothra as a diversion so that he can concentrate on luring all the 17 monsters.

The Monarch team follow Godzilla to Antarctica (Godzilla suddenly rises from his deep slumber in his sea lair and starts travelling towards Antarctica), where Jonah intends to free a three-headed Titan code-named "Monster Zero". Emma frees and awakens Monster Zero (controlling him with Orca after tuning its frequency to Zero's alpha frequency), which kills several Monarch members, including Dr. Graham, before battling Godzilla. Godzilla is swiftly defeated as its nuclear breath misses its mark and Monster Zero scores several directs hits with its electric lasers on Godzilla. The team realizes that Emma was not kidnapped by the terrorists but was secretly working with them. Emma contacts them and argues that the Titans must be awakened in order to heal the planet from damage that humans have caused. she argues that life sprouted wherever the monsters fought, caused by their radiation.

Jonah and Emma awaken Rodan (The Fire Demon) in Mexico. Monarch lures Rodan into fighting the approaching Monster Zero, but Monster Zero swiftly defeats Rodan before being ambushed by Godzilla, who severs one of its heads. During the fight, the Navy launches a prototype missile called the "Oxygen Destroyer", seemingly killing Godzilla. Monster Zero survives, regrows its lost head, and awakens all the other dormant Titans around the world, with Rodan submitting to its rule. Due to this, Madison disowns her mother.

Through mythological texts, Dr. Ilene Chen (Zhang Ziyi) discovers that Monster Zero is Ghidorah, an ancient alien seeking to Terraform the Earth. Mothra emerges from her cocoon and flies to Monarch's Bermuda base to communicate with Godzilla, who survived the detonation and is recuperating in an ancient underwater city. Via submarine, the team locates Godzilla's lair, where the whole area is highly radioactive. They deduce that it will take years for him to heal, and decide to detonate a nuclear warhead to fibrillate him. Dr. Serizawa sacrifices himself (Since the weapons system of the submarine was damaged) by manually detonating the weapon, which revives Godzilla and increases his power.

In Boston (In one of Monarch's "End of the world" bunkers where they are hiding), Emma realizes that the destruction Ghidorah and the other Titans will bring to the Earth is far worse than what humans could inflict, but Jonah ignores her pleas. Madison overhears this and steals the Orca. Madison broadcasts a frequency at Fenway Park that calms and unwittingly attracts the Titans to her location. Ghidorah lands in Boston to destroy the Orca, with Godzilla arriving with Monarch's assistance to engage it. Mark leads a team to rescue Madison and escape the city after learning that Godzilla's radiation levels are increasing and will lead to a thermonuclear explosion. Mothra arrives but is intercepted by Rodan, whom she defeats. Ghidorah overpowers Godzilla and prepares to kill him, but Mothra sacrifices herself and transfers her energy to Godzilla, rapidly healing him. Mark, Emma, and Madison are reunited and reactivate the Orca to lure Ghidorah away from Godzilla. Emma sacrifices herself, giving Mark and Madison time to escape. Godzilla enters a newly empowered state, glowing red and melting everything around him. He defeats Ghidorah with nuclear pulses and disintegrates the last head. Rodan and the other Titans converge on Godzilla and bow to him.

During the credits, news clippings and Monarch files show that the Titans are helping to heal the Earth, a suspected second Mothra egg has been discovered, some of the Titans are converging on Skull Island, and ancient cave paintings show Godzilla battling Kong. In a post-credits scene, Jonah and his forces purchase Ghidorah's remaining severed left head in Mexico.