Five years after the existence of the “Titans” was revealed to the world, Dr. Emma Russell, a paleobiologist working for the Titan-studying organization Monarch, and her daughter Madison witness the birth of a larva called Mothra. Emma calms Mothra using the “Orca,” a device that can emit frequencies to attract or alter Titan behavior. A group of eco-terrorists, led by former British Army Colonel Alan Jonah, attacks the base and kidnaps Emma and Madison, while Mothra flees and pupates under a nearby waterfall.
Monarch scientists Dr. Ishirō Serizawa and Dr. Vivienne Graham approach former employee Dr. Mark Russell, Emma’s ex-husband and Madison’s father, to help track them down. Mark is reluctant at first due to his hatred toward Godzilla, whom he blames for the death of his son during the events in San Francisco, but eventually agrees. The Monarch team follows Godzilla to Antarctica, where Jonah intends to free a three-headed Titan codenamed “Monster Zero”. Emma frees and awakens Monster Zero, who battles Godzilla, devours Graham and escapes. The team then learns that Emma is working with the terrorists. From a Monarch bunker in Boston, Emma contacts Monarch and argues that the Titans must be awakened in order to heal the Earth from the damages that humans have caused.
Emma awakens Rodan in Mexico. Monarch lures Rodan into fighting the approaching Monster Zero, but Monster Zero swiftly defeats Rodan before being ambushed by Godzilla, who severs his left head. During the fight, the U.S. Navy launches a prototype weapon called the “Oxygen Destroyer”, seemingly killing Godzilla. Unaffected, Monster Zero regrows his lost head and awakens all the other dormant Titans around the world, with Rodan submitting to his rule. Madison disowns Emma for her role in the destruction and deaths caused by the awakened Titans.
Through mythological texts, Dr. Ilene Chen discovers that Monster Zero is King Ghidorah, a prehistoric alien seeking to terraform the Earth to his liking. Mothra emerges from her cocoon and flies to Monarch’s Bermuda base to communicate with Godzilla, who is recuperating from the detonation in an ancient underwater city. Via submarine, the team locates Godzilla’s lair, which is highly radioactive. They deduce it will take far too long for Godzilla to heal on his own and decide to detonate a nuclear warhead to speed up the process. Serizawa sacrifices himself by manually detonating the warhead, reviving Godzilla and increasing his power.
Emma realizes the destruction Ghidorah and the other Titans will bring to the world is much worse than anything that humans could inflict, but Jonah ignores her pleas to stop. Madison overhears this and steals the Orca. Arriving at Fenway Park, Madison broadcasts a frequency that calms the Titans but unwittingly attracts all of them to her location. Ghidorah lands in Boston to destroy the Orca. Godzilla arrives with Monarch’s assistance to engage him in battle. Mark leads a team to rescue Madison and escape the city after learning Godzilla’s radiation levels are increasing and will lead to a thermonuclear explosion. Mothra arrives to help Godzilla but is intercepted by Rodan; she defeats him but is badly injured in the process.
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 to lead Ghidorah away, giving Mark, Madison, and Monarch time to escape. Godzilla enters a newly empowered state and defeats Ghidorah. Rodan and the other Titans converge on Godzilla and bow to him.
During the ending credits, news clippings and Monarch files show that the Titans are helping to heal the planet, a suspected second Mothra egg has been discovered, and some of the Titans are converging on Skull Island. Ancient cave paintings of Godzilla and Kong in battle are shown. In a post-credits scene, Jonah and his forces purchase Ghidorah’s severed left head in Mexico.