Heltene i det cryptozoologiske agentur Monarch står over for historiens største monstre, hvor Godzilla konfronterer giganterne Mothra, Rodan og den trehovedede King Ghidora. Menneskehedens eksistens står på spil, når vi genser de forhistoriske superarter, som alle troede, var myter.
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.