Charlize Theron plays Jill Young who as a child has witnessed the death of her mother, Ruth Young (Linda Purl), and the mother of Joe, a baby gorilla, at the hands of poachers led by Andrei Strasser (Rade Šerbedžija). Strasser loses his right thumb and trigger finger to Joe, and swears revenge on Joe for the damage. Before she dies, Ruth tells Jill to take care of Joe, to which Jill agrees. Twelve years later, Jill has raised Joe (who, because of a rare genetic anomaly, has grown to the size of 15 feet (4.6 meters) and weighs 2000 pounds (910 kilograms); as a result, the other gorillas won't accept him) and both are living in relative peace until a wildlife refuge director, Gregg O'Hara (Bill Paxton), convinces Jill that they would be safer from poachers if they relocate to the United States.
The trio go to Hollywood in Los Angeles, California (just like in the original film) and win the hearts of the refuge staff. There, Jill is approached by Strasser -- now running a fake animal preserve while really selling the animal organs off on the black market -- who has seen a news report about Joe and wants revenge because of the damage done to his hand 12 years ago. Jill fails to recognize Strasser as the poacher who killed both her mother and Joe's, since Strasser hid his right hand in his coat pocket. Strasser tries to persuade Jill that Joe would be better off in his wildlife refuge back in Africa. Later, during a gala, Strasser's henchman, Garth, uses a poacher's noisemaker to scare Joe into a frenzy. Joe trashes the gala, recognizes Strasser and tries to attack him. Joe is tranquilized and placed in a concrete bunker. Before their departure, Gregg has fallen in love with Jill and he kisses her goodbye.
When Jill learns that Joe may be euthanized she decides to take Strasser's offer. She and the refuge staff smuggle Joe out in a truck. On the way to the airport, Jill notices Strasser's missing fingers. It makes her realize that he is the poacher who killed both her mother and Joe's. She briefly fights with Strasser and Garth, then jumps from the truck and into the street. Joe sees her and topples the truck over on its side and escapes. Meanwhile, Gregg has realized that Strasser is a poacher and goes after both Jill and Joe. He finds Jill, who reveals to Gregg that Strasser killed her mother and plans to kill Joe. They locate Joe at a carnival where he is playfully wreaking havoc. Strasser arrives and attempts to shoot Jill. But Garth pushes Strasser's gun away from Jill, causing him to fire at a spotlight, which starts a fire and causes the Ferris wheel to break down. Realizing how ruthless Strasser truly is, Garth says that he quits, but Strasser knocks Garth unconscious with his gun. Strasser eventually confronts Jill and attempts to kill her, but Joe sneaks up behind them and tosses Strasser onto some electrical wires where he is killed by electrocution. In a poignant scene at the Santa Monica Pier, while saving a child, Joe falls from the collapsing Ferris wheel (the scene is reminiscent of King Kong falling from the Empire State Building). Joe survives the fall and is shipped back to Africa to run free on his own refuge funded by donations from the various people who witnessed his heroism at the wheel.
- Bill Paxton as Professor Gregory "Gregg" O'Hara - He is a wildlife teacher who comes to Africa to study animals and befriends Jill Young.
- Charlize Theron as Jill Young - She is a young woman who raised Joe since he was a baby after their mothers were killed by poachers.
- John Alexander as Mighty Joe Young - He is a big gorilla who is brought to California to be safe from poachers.
- Rade Šerbedžija as Andrei Strasser - He is the poacher who killed both Joe's and Jill's mothers.
- Regina King as Cecily Banks - She is a doctor at the Animal Preserve in California where Joe is brought to.
- Peter Firth as Garth - Strasser's right hand man
- Naveen Andrews as Pindi - Gregg O'Hara's guide to Africa.
- David Paymer as Harry Ruben - .
- Robert Wisdom as Kweli
- Christian Clemenson as Jack
- Geoffrey Blake as Vern
- Lawrence Pressman as Doctor Elliot Baker
- Linda Purl as Doctor Ruth Young
- Mika Boorem as Young Jill Young
- Cory Buck as Jason a Little Boy Who that Joe Save Him
- Liz Georges as Jason's Mother
- Ray Harryhausen as Gentleman at Party - Harryhausen was an animator for the original Mighty Joe Young.
- Terry Moore as Elegant Woman at Party - Moore starred as Jill Young in the original Mighty Joe Young.
- This was the first time since Peter Pan in which Disney collaberated with RKO, only this time, the latter is demoted to a producer, while Buena Vista is the then distributor.
- This was the one Disney remake of a non-Disney movie, alongside Jungle 2 Jungle (Un indien dans la ville).
Mighty Joe Young had a better critical reception than the other big monster remake of the year, Godzilla; however it was ultimately judged a disaster by some critics as being typically 'Disney' in plot and outcome. The movie holds a rating of 51% from Rotten Tomatoes. The movie grossed $50,632,037 with a production budget of $90 million thus a box office bomb.
Mighty Joe Young received an Academy Award nomination for Best Visual Effects, losing to What Dreams May Come.
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