In New York Harbor, Carl Denham (Robert Armstrong), a filmmaker famous for shooting animal pictures in remote and exotic locations, charters the ship Venture for his new project, but he is unable to secure an actress. Talent agent Charles Weston refuses to supply anyone because of the dangerous nature of the expedition, so Carl searches the streets of New York for a suitable woman. He chances upon starving, unemployed Ann Darrow (Fay Wray) and convinces her to join him on the adventure of a lifetime, offering her the lead in his project. They steam for weeks in the direction of Indonesia, the general region in which Denham claims they will make the planned motion picture. Despite his ongoing declarations that women have no place onboard ships, the ship's first mate, Jack Driscoll (Bruce Cabot) is obviously becoming attracted to Ann.
After maintaining secrecy for weeks, Denham finally tells Driscoll and Captain Englehorn (Frank Reicher) that they're searching for an uncharted island shown on a map in Denham's possession. Denham then describes something monstrous connected to the island, a legendary entity known to the islanders only as "Kong." As Venture steams through the fog surrounding the island, the crew hears drums in the distance. Arriving at the island's shore, they see a native village on a peninsula, cut off from the bulk of the island by an enormous stone wall. A landing party, including the filming crew and Ann, goes ashore and encounters the natives, who are about to hand over a woman to Kong as a ritual sacrifice. The native chief (Noble Johnson) spots them, gets a clear look at Ann, and proposes to trade six native women for her. Denham declines, as he and his party edge away from the scene, assuring the chief that they will return tomorrow to get better acquainted.
However, later that night, a contingent of natives captures Ann and takes her through the wall, where, left tied to columns, she is presented to Kong. Soon after, Kong, a giant gorilla, emerges through the trees and carries Ann into the jungle. The Venture crew returns to the village and opens the huge gate on the wall; half of the crew then goes after Kong in hopes of rescuing Ann. While trekking through the dense jungles, the crew discovers that, in addition to Kong, other giant creatures inhabit the island. They encounter an enraged Stegosaurus, (which they kill); a lethal Brontosaurus (which capsizes their raft, killing several of the crew and causing them to lose their weapons); and, eventually, Kong himself, who prevents the men from following him across a ravine by shaking them off a fallen log bridge. Only Driscoll and Denham are left alive.
When a Tyrannosaurus rex attempts to eat Ann, Kong departs the ravine to fight the carnivore, killing it by breaking its jaw and neck with his bare hands. Driscoll continues to pursue Kong and Ann while Denham returns to the village for more men and weapons. The giant ape takes his captive to his cave at the summit of Skull Mountain, where she is newly menaced by a snake-like Elasmosaurus, drawing Kong into another battle to the death to save Ann. Driscoll sneaks into the cave as Kong takes Ann to a promontory and begins inspecting her. He then hears noises made by Driscoll inside the cave and goes to investigate. While Kong is away, Ann tries to escape but is attacked by a Pteranodon. Again, Kong is alerted, and he snatches the Pteranodon out of the air, freeing Ann from its clutches. After winning this latest battle, Kong inspects the dead Pteranodon while Driscoll and Ann use this distraction to escape by climbing down a vine dangling from the cliff's edge. Kong discovers the escape and starts pulling the vine back up. Ann and Driscoll let go, falling into a river and making it back to the village, but not without an angry Kong on their trail. The ape breaks through the large gate in the wall, and storms the village, killing many natives. Denham hurls a gas bomb at Kong, knocking him out, whereupon he exults in the opportunity presented: "We're millionaires, boys! I'll share it with all of you! Why, in a few months, his name will be up in lights on Broadway! Kong! The Eighth Wonder of the World!"
In Manhattan, "The Eighth Wonder of the World!" appears in lights on a marquee. Along with hundreds of curious New Yorkers, Denham, Driscoll, and Ann are dressed in evening wear for the gala event. The curtain lifts, and Denham presents Kong, subdued and shackled, to the stunned audience. All goes well until news photographers snap photographs, and their cameras' flashbulbs make Kong think that the photographers are harming Ann. Kong breaks free of his bonds and escapes from the theater as the screaming audience flees. Kong rampages through city streets, causing many casualties. He climbs a hotel and spots Ann in an upper-floor room. His massive hand smashes through the window, knocking a defending Driscoll to the floor unconscious. Kong grabs Ann and continues his rampage, destroying an elevated train. He eventually climbs the Empire State Building, still holding Ann. Listening to distressing radio reports about Kong's progress, Driscoll seizes on the idea of using planes to shoot him atop the skyscraper. The police call the field to order the air assault while Driscoll and Denham race to the Empire State Building.
A squadron of military biplanes swoops on Kong as he reaches the top of the skyscraper. Kong manages to knock one plane out of the sky, but the others rake him with machine gun fire, careful to shoot only when the giant ape has placed Ann on a lower ledge. Kong is mortally wounded. He looks at Ann one last time before falling to his death. Defying police orders not to enter the building during the battle, Driscoll arrives at the ledge and takes Ann in his arms. Below on the street, Denham makes his way through the gathered crowd to look upon the fallen Kong. A police lieutenant says, "Well, Denham, the airplanes got him." The film ends with Carl Denham's famous reply, "Oh, no, it wasn't the airplanes...it was Beauty killed the Beast."