Will Rodman (James Franco) is a scientist who lives in San Francisco with his father Walter (John Lithgow), who has Alzheimer's Disease. Will works for a major pharmaceutical company called GenSyn Laboratories, developing a serum know as ADV 112, which might be able to cure his father's illness.
The serum is tested on a group of apes brought from Africa. One of them, a female know as "Bright Eyes", is pregnant and soon gives birth to a male Chimpanzee. Wanting to protect him from the scientists, she attacks them and, in the process, all the apes escape, ruining Will's chances of convincing GenSyn's board of directors to move on to human tests. All the apes are put down and all samples of the serum are destroyed, but Bright Eye's son is hidden by Will's friend Franklin (Tyler Labine), who convinces Will to raise it.
Will calls the ape "Caesar" and they become great friends. Caesar grows up and displays heightned intelligence, due to her mother's serum-filled blood running through his veins. One day, Walter accidentally leaves Will's house and is nearly ran over by a neighboor, Hunsiker (David Hewlett) who becomes hostile towards Walter. Caesar tries to defent him, but accidentally mauls Hunsiker and Will is forced by the police to send Caesar to an Ape Sanctuary called "The Ranch", ran by Mr. Landon (Brian Cox).
There, Caesar befriends an Orangutan called Maurice and a Gorilla called Buck. After a brief confrontation, he replaces a Gorilla called Rocket as the Ranch's Alpha Male and finds a mate in a Chimpanzee called Cordelia. Caesar intelligence continues to grow, and he is soon at odds with Mr. Landon's sadistic employee Dodge (Tom Felton), who verbally and physically abuses the apes.
Meanwhile, Will convinces his friend Edward Jacobs (David Oyelowo) to restart the ADV 12 project based on the progress displayed by Caesar and Walter, who had been injected with a sample of the drug that Will kept and was actually cured for two years. They bring a new batch of apes to be tested on, and one of them, Koba, soon reveals himself to be evil. In exchange, Will wants Caesar to be released from the Ranch.
There, Caesar becomes convinced that Will betrayed him. He also discovers that, by drinking his blood, other apes can become as smart as he is. Caesar soon organizes the apes in an army and escapes, going to GenSyn and releasing all the apes therein, including Koba, who murders Franklin. Will believes Caesar to be responsible and goes after him with his co-worker and girlfriend, Caroline Stewart (Freida Pinto).
The apes attack San Francisco, fighting the police, and release all the apes from the San Francisco Zoo. They make their way to the Golden Gate Bridge, fighting the police and a revengeful Dodge, who is killed by the Gorillas after killing Rocket. The apes overpower the humans and take shelter at the Muir Woods on the other side of the Bridge.
Will convinces the police to allow him to go there alone and reason with Caesar, but they betray him and attack the ape reserve. In the ensuing battle, Will takes a bullet meant for Caesar and dies. The humans are defeated and driven away from the forest by Caesar and his army.
Shortly thereafter, it is revealed that Koba had a flu upon being experimented on, and the serum turned it into a powerful airborne biological agent that already infected several people in San Francisco. When they leave the city in fear of the apes, they accidentally spread the virus all over the world. In less than a year, Humanity is nearly extinct. Caesar, who had been watching over the events, decides that it is time for apes to take over the world and cage humans much like they once caged apes.
Earth is now their planet.