The film opens in New York City, 1933, at the height of the Great Depression. Having lost her job as a vaudeville actress, Ann Darrow is hired by troubled filmmaker Carl Denham to be an actress in his new motion picture against the famous and popular actor Bruce Baxter. With time running out, Ann signs on when she learns her favourite playwright Jack Driscoll is the screenwriter. On the SS Venture, they slowly fall in love. As for Carl, a warrant is out for his arrest and Captain Englehorn begins to have second thoughts, following the fears of his crew over the legend of Skull Island. Despite his attempt to turn around, their ship is sucked up into a fog and crashes into one of the encircling rocks.
Carl and his crew explore the island, with a deserted village against a wall, but they are attacked by the vicious natives. Mike, the sound technician, is speared, one of the sailors has his head crushed, and Jack is knocked out. Ann screams, and a roar beyond the wall responds. The matriarch vows to sacrifice her to "Kong", a 25 ft (7.6 m) gorilla. Englehorn and his crew break up the attack and return to the damaged ship. They finally lighten the load to steer away, until Jack discovers Ann has been kidnapped. On the island, Ann is hung from a balcony to the other side of a valley. The crew comes armed, but are too late. Carl sees the gorilla that has taken her. Englehorn gives them 24 hours to find her. In the meantime, Ann discovers the remains of the previous sacrifices, and stabs Kong's hand with her ceremonial necklace to no avail. Kong takes Ann into the jungles of the island.
Captain Englehorn organises a rescue party to find Ann and hunt down the beast. The rescue party is caught up in a Venatosaurus pack's hunt of Brontosaurus, and four of them (including Herb, the cameraman) are killed while Jack and the rest of the crew survive. Ann manages to entertain Kong with juggling and dancing, but he does not kill her when she refuses to continue, leaving her instead. The rest of the rescue party come across a swamp. It is here that Bruce Baxter and two others leave the group. The survivors stumble across a log where Kong attacks, shaking them off the log into a ravine. He returns to rescue Ann from three Vastatosaurus Rex (modern Tyrannosaurus), and takes her up to his mountain lair. While there, Ann briefly attempts to communicate with Kong using sign language, but without success. Englehorn and the rest of the crew rescue whomever is left of the rescue party from the pit of giant insects, and as Jack decides to continue to search for Ann, Carl decides to capture Kong. Jack comes to Kong's lair, and disturbs him from his slumber. As Kong fights a swarm of giant bats, Ann and Jack escape by grabbing the wing of a Terapusmordax and then jumping to a river. They arrive at the village wall with the angry Kong following them, where Ann becomes distraught by what Carl plans to do. Kong bursts through the gate and struggles to get her back, killing several sailors, but is subdued when Carl knocks him out with Chloroform.
In New York around Christmas, Carl presents Kong — the Eighth Wonder of the World on Broadway. Ann has become an anonymous chorus girl and a double of her is used as a replacement in the play however Kong becomes enraged from the fake 'Ann' and breaks free from his chrome-steel chains. Causing chaos throughout the town searching for Ann by picking up several look alikes, Jack looks him in the eye and a chase through the streets. Kong eventually knocks Jack out by stopping the taxi he is fleeing in and flipping it, then encounters Ann again. They share a quiet moment on a frozen lake in Central Park before they are interrupted by the military. Kong climbs onto the Empire State Building, and observing the dawning day repeats the sign for "beautiful" Ann had used in his lair, causing a shocked Ann to realize his intelligence. Before Ann is able to attempt further communication they are again attacked and Kong makes his last stand against the Curtiss Helldivers, downing three of them. Ultimately Kong is hit by several bursts of gunfire from the surviving planes, and gazes at a distraught Ann for the last time before falling off the building to his death. Ann is greeted by Jack, and the reporters flood to Kong's corpse. Carl takes one last look and says, "It wasn't the airplanes. It was Beauty killed the Beast."
- Naomi Watts as Ann Darrow: A struggling vaudeville actress who is desperate to continue acting. Carl Denham discovers her attempting to steal an apple from a fruit stand, only to pay for it himself. She is a big fan of Jack Driscoll, but knows nothing about acting in a movie. During the course of the voyage, she falls in love with Driscoll. She also forms a special relationship with Kong. Ann herself is very confident, beautiful, and capable of handling herself in a tough situation.
- Jack Black as Carl Denham: A film director who obtained the map to Skull Island. Due to his desperate situation — involving debts and theft — Carl is obsessive and slowly loses his moral compass during the film. His producers are convinced that he is on a wild goose chase and the police have a warrant for his arrest.
- Adrien Brody as Jack Driscoll: A scriptwriter who falls for Ann. He is on the voyage mistakenly, when he delivers 15 pages of script to Denham, who consequently delays him as the SS Venture begins its voyage. Jack is quickly enchanted by Ann's beauty and charm, and plans to write a play for her. He refuses to give up on Ann's rescue, even continuing on alone even when the crew turns back. He is heavily involved with Kong's return to Manhattan.
- Thomas Kretschmann as Captain Englehorn: The German Captain of the SS Venture, who Denham has hired to take the film crew to Skull Island.
- Colin Hanks as Preston: Denham's neurotic but honest personal assistant.
- Jamie Bell as Jimmy: A boy who was found on the SS Venture, wild and abandoned. He is a kleptomaniac and views Hayes as a father figure.
- Evan Parke as Ben Hayes: Englehorn's first mate and a friend of Lumpy, who leads Ann's rescue mission due to his army training and combat experience gained during World War I. He is killed during the log scene after Kong snatches him and subsequently throws him against the rock wall. In the extended cut, Jimmy takes his hat in remembrance after the group is rescued from the insect pit.
- Lobo Chan as Choy: Lumpy's best friend and a janitor on the Venture, who falls to his death during the log scene.
- Kyle Chandler as Bruce Baxter: An actor who specialises in adventure films such as Tribal Brides of the Amazon, Rough Trader, and Dame Tamer. He abandons Ann's rescue mission but brings Englehorn to rescue them from the insect pit, and is given credit for rescuing Ann during the Broadway display of Kong. He has sense once more to leave before Kong escapes.
- Andy Serkis as Kong (motion capture and voice): The movies main star and titular character, Kong is a 25-ft gorilla who is around 120–150 years old. He is the last of his species, Megaprimatus kong.
- Andy Serkis as Lumpy: The ship's cook, barber and surgeon. He is a brave sailor who goes to search for Ann but is eaten alive in the pit after fighting a group of Carnictis.
- John Sumner as Herb: Denham's loyal camera man who has a fake right leg. He is killed by a pack of Venatosaurus after the Apatosaurus stampede.
- Craig Hall as Mike: Denham's soundman for the journey and ends up being the first person to be killed by the Skull Island natives when a spear impales him.
- Jed Brophy and Todd Rippon cameoed as crew members.
The marketing campaign for King Kong started in full swing on June 27, 2005, when the teaser trailer made its debut, first online at the official Volkswagen website at 8:45 p.m. EST, then 8:55 p.m. EST across media outlets owned by NBC Universal (the parent of Universal Studios), including NBC, Bravo!, CNBC and MSNBC. That trailer appeared in theatres attached to War of the Worlds, which opened on June 29.
Jackson also regularly published a series of 'Production Diaries', which chronicled the making of the film. The diaries started shortly after the DVD release of The Return of the King as a way to give Jackson's The Lord of the Rings fans a glimpse of his next project. These diaries are edited into broadband-friendly installments of three or four minutes each. They consist of features that would normally be seen in a making-of documentary: a tour of the set, a roving camera introducing key players behind the scene, a peek inside the sound booth during last-minute dubbing, or Andy Serkis doing his ape movements in a motion capture studio. The production diaries were released on DVD on December 13, 2005, one day before the U.S. release of the film. This was one of the first occasions in which material that would normally be considered supplementary to the DVD release of a film, was not only released separately, but done so in a prestige format; the Production Diaries came packaged in a box with a set of prints and a replica 1930s-era clipboard. It is also the first time such material was published prior to the release of the film.
A novelization of the movie and a prequel entitled The Island of the Skull was also written. A multi-platform video game entitled Peter Jackson's King Kong: The Official Game of the Movie was released, which featured an alternate ending. There was a hardback book entitled The World of Kong, featuring artwork from Weta Workshop to describe the fictional bestiary in the film. A number of spin-offs from the remake's franchise include books, novels, comics and video games.
- Director Peter Jackson originally wanted actress Fay Wray, who played Ann Darrow in the original 1933 King Kong, to make a cameo at the end of the film and deliver the iconic line "It was beauty killed the beast." However, Wray passed away before filming, and the line was delivered by the character of Carl Denham instead, as in the original film. A reference is made to Fay Wray in the film, when Carl Denham mentions that "Fay was unavailable" when discussing actresses for his picture.