Els criptozoòlegs de l'agència Monarch s'enfronten a un grup de monstres enormes: Godzilla, Mothra, Rodan i l'enemic de la humanitat, King Ghidorah. Aquestes criatures grans faran tot el possible per sobreviure, posant en risc l'existència de l'ésser humà al planeta.
A 17th-century Caribbean port rumored to have frequented by pirates rises from the ocean floor, where it came to rest after an earthquake many years before. A scientist wants to study it, some thugs want the treasure alleged to be stored there, a bunch of mutated giant crabs living there attack them all.