In 1933, during the Great Depression, New York City vaudeville actress Ann Darrow is hired by financially troubled filmmaker Carl Denham to star in a film alongside actor Bruce Baxter. Ann learns her favorite playwright, Jack Driscoll, is the screenwriter. Filming takes place on a tramp steamer, the SS Venture, under the command of Captain Englehorn, and under Carl's pretense that it will be sailing to Singapore. In truth, Carl intends to sail to and film the mysterious Skull Island. Captain Englehorn has second thoughts about the voyage, prompted by his crew's speculation of trouble ahead. On the voyage, Ann and Jack fall in love. Deep in the southern waters, the Venture receives a radio message informing Englehorn there is a warrant for Carl's arrest due to his defiance of the studio's orders to cease production. The message instructs Englehorn to divert to Rangoon, but the ship becomes lost in fog and runs aground on the rocky shore of Skull Island. Carl and his crew explore the island and are attacked by natives. Ann screams as she is captured, and a loud roar is heard beyond a wall. After this, the matriarch of the tribe targets Ann, muttering the word "Kong". Englehorn intervenes and rescues the film crew, but as they make efforts to leave the waters, a native sneaks onto the ship and kidnaps Ann. The natives offer Ann as a sacrifice to Kong, a 25 feet (7.6 m) tall gorilla. Jack notices Ann's disappearance, and the crew returns to the island, but are too late as Kong takes Ann and flees into the jungle. Carl manages to catch a glimpse of Kong, and becomes more determined to capture him on film.

Though initially terrified of her captor, Ann wins Kong over with juggling and dancing, and begins to grasp Kong's intelligence and capacity for emotion. Englehorn organizes a rescue party, led by his first mate Hayes and Jack, and accompanied by the film crew. The party is then caught in the middle of a pack of Venatosaurus saevidicus and the herd of Brontosaurus they are hunting, and several are killed in the resulting stampede. After this, Baxter leaves the group to return to the ship. The rest of the rescue party continues through the jungle, when Kong attacks and throws them into a ravine. Kong returns to Ann and rescues her from three Vastatosaurus rex, before taking her to his lair in the mountains. The remaining rescue party are attacked by giant insects in the ravine, and are rescued by a returning Baxter, along with Englehorn. As Jack continues searching for Ann, Carl decides to capture Kong. Jack goes to Kong's lair, inadvertently waking him and provoking a swarm of flying Terapusmordax. As Kong fights the swarm, Ann and Jack escape. They arrive at the wall with Kong pursuing them, and Ann becomes distraught by what Carl plans to do. Kong bursts through the gate and attempts to get her back, killing several sailors, but is subdued when Carl knocks him out with chloroform.

In New York City, Carl presents "Kong, the Eighth Wonder of the World" on Broadway, starring Baxter and an imprisoned Kong. Ann is played by an anonymous chorus girl, as she refused to take part in the performance. Agitated by the flashing of the cameras, Kong breaks free from his chrome-steel chains and wrecks the theater. He chases Jack out into the metropolitan streets and begins a search for Ann. Kong knocks Jack out, then encounters Ann again, who is able to calm him. Kong and Ann share a moment on a frozen pond in Central Park until the U.S. Army attacks. Kong climbs with Ann onto the top of the Empire State Building, where he fights off six F8C-5 Helldiver Navy planes. Kong is mortally wounded by the planes' gunfire, and gazes at Ann for the last time before dying and falling from the building. As Ann is reunited with Jack, civilians, policemen, and soldiers gather around Kong's corpse. Carl makes his way through the crowd, takes one last long look at Kong and says, "It wasn't the airplanes. It was Beauty killed the Beast."