The year is 1932. In New York Harbor, filmmaker Carl Denham, famous for making wildlife films in remote and exotic locations, charters Captain Englehorn's ship, the Venture, for his new project. However, he is unable to secure an actress for a female role he has been reluctant to disclose. Searching in the streets of New York City, he finds Ann Darrow and promises her the adventure of a lifetime. The crew boards the Venture and sets off, during which the ship's first mate John Driscoll, falls in love with Ann.

Denham reveals to the crew that their destination is in fact Skull Island, an uncharted territory. He alludes to a monstrous creature named Kong, rumored to dwell on the island. The crew arrives and anchor offshore. They encounter a native village, separated from the rest of the island by an ancient stone wall. They witness a group of natives preparing to sacrifice a young woman termed the "bride of Kong". The intruders are spotted and the native chief stops the ceremony. When he sees Ann, he offers to trade six of his tribal women for the "golden woman". They rebuff him and return to the Venture.

That night, the natives kidnap Ann from the ship and take her through the wall gate and to an altar, where she is offered to King Kong, an enormous gorilla-like creature. Kong carries Ann into the wilderness as Denham, Driscoll and some volunteers enter the jungle in hopes of rescuing her. They are ambushed by another giant creature, a Stegosaurus, which they manage to defeat. After facing a Brontosaurus and Kong himself, Driscoll and Denham are the only survivors.

A Tyrannosaurus rex attacks Ann and Kong, but he kills it in the battle. Meanwhile, Driscoll continues to follow them, while Denham returns to the village for more men. Upon arriving in Kong's lair, Ann is menaced by a snake-like Elasmosaurus, which Kong also kills. While Kong is distracted killing a Pteranodon that tried to fly away with Ann, Driscoll reaches her and they climb down a vine dangling from a cliff ledge. When Kong notices and starts pulling them back up, the two fall unharmed. They run through the jungle and back to the village, where Denham, Englehorn, and the surviving crewmen are waiting. Kong, following, breaks open the gate and relentlessly rampages through the village. Onshore, Denham, now determined to bring Kong back alive, knocks him unconscious with a gas bomb.

Shackled in chains, Kong is taken to New York City and presented to a Broadway theatre audience as "Kong, the Eighth Wonder of the World". Ann and John are brought on stage to join him, surrounded by a group of press photographers. Kong, believing that the ensuing flash photography is an attack, breaks loose. The audience flees in horror. Ann is whisked away to a hotel room on a high floor, but Kong, scaling the building, soon finds her. His hand smashes through the hotel room window, immobilizing John, and abducts Ann again. Kong rampages through the city. He wrecks a crowded elevated train and then climbs the Empire State Building. At its top, he is attacked by four airplanes. Kong destroys one, but finally succumbs to their gunfire. He gazes at Ann one last time before falling to his death. Ann and John are reunited. Denham arrives and pushes through a crowd surrounding Kong's corpse in the street. When a policeman remarks that the planes got him, Denham tells him, "No, it wasn't the airplanes. It was Beauty killed the Beast".