In present-day San Francisco, pharmaceutical chemist Will Rodman is testing the viral-based drug ALZ-112 on chimpanzees at the biotech company Gen-Sys to find a cure for Alzheimer's disease. ALZ-112 is given to a chimp named Bright Eyes, greatly increasing her intelligence. However, during Will's presentation for the drug, Bright Eyes is forced from her cage, goes on a rampage and is shot to death. Will's boss Steven Jacobs terminates the project and has the chimps euthanized. However, Will's assistant Robert Franklin discovers that the reason for Bright Eyes' rampage was that she had recently given birth to an infant chimp. Will reluctantly agrees to take in the chimp, eventually giving him the name “Caesar.” Discovering that Caesar has inherited his mother's intelligence through being exposed to ALZ-112 in her womb, Will decides to raise him. Three years later, Caesar has become a highly intelligent animal because of the ALZ-112, and can play games, draw pictures, and communicate with Will through sign language. Will soon introduces Caesar to the redwood forest at Muir Woods National Monument. Meanwhile, Will treats his dementia-suffering father Charles Rodman with ALZ-112, which seems to restore his cognitive ability.
Five years later, Caesar, now a young adolescent, questions his identity and learns of his origins from Will. Meanwhile, Charles' condition returns as his immune system becomes resistant to ALZ-112. Caesar injures an aggressive neighbor, Douglas Hunsiker, while defending a confused Charles from him. He is taken to a primate shelter. Because of his increased intelligence and his different appearance to the other apes, Caesar is tormented by the alpha chimp named Rocket and the chief guard, Dodge Landon. However, Caesar also befriends a former circus orangutan named Maurice, who also knows sign language. Caesar learns how to unlock his cage, gaining free access to the common area. With the assistance of a gorilla named Buck, he confronts Rocket and claims the position of alpha chimp. Meanwhile, Jacobs clears the development of a more powerful, gaseous version of the drug – ALZ-113 – when Will tells him it can also improve intelligence. Will takes the drug home to try to save his father, but Charles declines further treatment and dies overnight.
After attempting to test the drug on a scarred bonobo test subject named Koba, Franklin becomes exposed to ALZ-113 and becomes ill. Attempting to warn Will at his home, he sneezes blood onto Hunsiker and is later discovered dead. Will attempts to reclaim Caesar, but Caesar instead decides to stay and uses the ALZ-113 canisters from Will's house and enhances the intelligence of the other apes in the sanctuary. When Dodge attempts to get him back into his cage, Caesar speaks for the first time, shouting "No!" and fights with Dodge while freeing the apes, which inadvertently leads to Dodge's death. The apes flee the facility, releasing Koba and the remaining apes from Gen-Sys, and free more apes from the San Francisco Zoo.
A battle ensues as the ape “army” fights their way past a police blockade on the Golden Gate Bridge in an attempt to escape into the redwood forest. Buck jumps into a police helicopter in which Jacobs is riding to rescue Caesar, at the cost of his life. Koba then pushes Jacobs into the Golden Gate strait to his death after the crash. As the apes find their way into the forest, Will catches up to them in a stolen police car and warns Caesar that the humans will hunt them down and begs him to return home. In response, Caesar hugs him and says, "Caesar is home". Will, realizing that this is indeed their last goodbye, respects Caesar's wishes. The apes embrace their new lifestyle in the forest as news and police helicopters fly over San Francisco.
Meanwhile, Hunsiker, now infected with ALZ-113, arrives at San Francisco International Airport for his flight to Paris. He eventually spreads the virus around the globe via international flight routes, leading to a deadly pandemic.
James Franco as Dr. William "Will" Rodman,
Freida Pinto as Dr. Caroline Aranha,
John Lithgow as Charles Rodman,
Brian Cox as John Landon,
Tom Felton as Dodge Landon,
David Oyelowo as Steven Jacobs,
Andy Serkis as Caesar,