In 1933, during the Great Depression, New York City 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 the SS Venture, under 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. 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 Skull Island. Carl and his crew explore the island and are attacked by natives who kill two members of the crew. 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-foot-tall (7.6 m) gorilla. Jack notices Ann's disappearance, and the crew returns to the island, but are too late as Kong flees with Ann into the jungle. Carl manages to catch a glimpse of Kong and becomes determined to capture him on film.

Though initially terrified of her captor, Ann wins Kong over with her juggling and dancing skills and begins to grasp Kong's intelligence and capacity for emotion. Englehorn organises a rescue party, led by his first mate Hayes and Jack, and accompanied by the film crew. The party is caught in the middle of a pack of Utahraptor-like Venatosaurus saevidicus and the herd of Brontosaurus they are hunting, with several killed in the resulting stampede. After this, Baxter leaves the group to return to the ship.

The remaining members of the party continue through the jungle when Kong attacks, making them fall into a ravine resulting in Hayes' death and Carl losing his camera. Kong returns to Ann and saves her from three dinosaurs, before taking her to his lair in the mountains. The remaining rescue party are attacked by giant insects in the ravine and rescued by Baxter and 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 large bat-like creatures. As Kong fights them off, 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 to get Ann 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 chains and wrecks the theater. He chases Jack out into the metropolitan streets and searches for Ann. Kong knocks Jack unconscious, 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 Navy planes. Kong is mortally wounded by the planes' gunfire and falls from the building. As Jack takes an elevator to the top of the building and reunites with Ann, civilians, policemen, and soldiers gather around Kong's corpse in the street. One bystander comments that the airplanes got him. Carl makes his way through the crowd, takes one last look at Kong and says, "It wasn't the airplanes. It was Beauty killed the Beast."