A female chimpanzee is among those captured for a drug trial in San Francisco, where she’s named Bright Eyes by the lead scientist Will Rodman and animal handler Robert Franklin. Will is searching for a cure to Alzheimer’s due to his father Charles being afflicted with it, and Bright Eyes quickly shows increased intelligence after being given a new drug, ALZ-112. Unfortunately, she also aggressively escapes her cell and goes on a rampage until security puts her down right in the middle of a presentation to investors, leading Will’s boss Steven Jacobs to order the trial ended and all the chimps put down. Will and Franklin discover Bright Eyes had actually just given birth and was protecting her son, and Will takes him home intending to find an animal shelter to take him.
That stay turns into years when the baby chimp, named Caesar by Charles, quickly shows signs of even greater intelligence due to being in utero when his mother was given 112. After three years he has a sophisticated sign language vocabulary and intelligence of a human several years older, and Will is driven to steal some 112 to give to his father. The drug has an immediate effect, but at the same time Caesar escapes the house and is injured by their neighbor Hunsiker who thinks he’s dangerous. Will takes him to zoo vet Caroline Aranha, who is quickly taken with Caesar’s intelligence and suggests they take him on periodic trips to Muir Woods.
Five years later, Will and Caroline are dating and the adult Caesar is now asking questions about his past. Will shows him the lab and reveals the truth about Bright Eyes to both Caesar and a disapproving Caroline. Charles quickly regresses as his system produces antibodies to counteract 112, and in his confused state gets into Hunsiker’s car and crashes it. Hunsiker’s angry confrontation over it provokes Caesar, who furiously attacks him in front of the whole neighborhood, causing a court order for him to be taken to the San Bruno Primate Shelter.
The shelter’s owner John Landon assures Will and Caroline that Caesar will be well taken care of, but in fact he’s left to the mercy of John’s sadistic son Dodge, and also runs afoul of the alpha male chimp Rocket. Meanwhile, Will convinces Jacobs to let the testing resume on a more virulent strain, 113, using a bonobo named Koba who is already horrifically scarred from numerous other experiments. The new drug proves to work, but in the process, Franklin accidentally breathes it in and becomes extremely sick. Charles also asks Will to let him go, and peacefully passes away in his sleep.
Caesar finds he can communicate with the orangutan Maurice, who knows sign language from his time in the circus, and is able to steal a pocket knife from a friend of Dodge’s who is illegally shown around the place. He uses it to pick his cage lock and frees the gorilla Buck who has been kept in his cage for years, and arranges a fight with Rocket in front of the other apes that he quickly wins, becoming the new alpha male.
Will discovers Jacobs is expanding the 113 tests without proper precautions and quits in protest, followed by bribing John to let him take Caesar back. However, Caesar has grown disillusioned with humans and refuses to leave the other apes. He breaks out and gets a pair of 113 vials from Will’s house, spreading them throughout the apes’ cages. The next day they’ve all become intelligent, and during Dodge’s next abuse, Caesar shocks human and ape alike when he verbally shouts “NO!” He keeps shouting it as he frees all the apes, and finishes Dodge for good by spraying him with a fire hose while he’s holding an electrified prod. At the same time, Franklin desperately tries to see Will, and ends up sneezing blood onto Hunsiker. He dies in his apartment shortly afterward.
Upon discovering the female chimp Cornelia was taken to the lab, Caesar leads the apes there to free all the test subjects, including an especially enthusiastic Koba. After freeing more from the zoo, they go on a rampage across San Francisco, with Jacobs taking to a helicopter to direct the police response. The action ends up on the Golden Gate Bridge, where Caesar outsmarts the police by commandeering one of their horses, directing the rest to attack from above. Jacobs’ helicopter arrives and shoots at them, to which Buck sacrifices himself by jumping at it and causing it to crash. Jacobs survives the crash and is left begging Caesar to help him escape the dangling helicopter, but Caesar refuses and leaves the situation to Koba, who kicks Jacobs off the bridge to his death.
Will has been following the battle the whole time, and gets all the way into Muir Woods, where Koba jumps down and attacks him. Caesar soon arrives and tells Koba to leave, and when Will tells him to stop and come back home, whispers to him “Caesar is home.” Will accepts it and watches the apes climb the redwoods to their freedom.
Hunsiker arrives at his job as a pilot, resulting in 113 being spread across the world, and the death of most of humanity as the world is left to its new masters, the apes.
