Will Rodman, a scientist at biotechnology company Gen-Sys, is testing viral-based drug ALZ-112 on chimpanzees to find a cure for brain ailments such as Alzheimer's disease. The drug is given to a chimpanzee, Bright Eyes, greatly increasing her intelligence, but she is forced from her cage, goes on a rampage, and is killed. Will's boss Steven Jacobs terminates the project and orders chimp handler Robert Franklin to euthanize the chimps. After doing as ordered, Franklin discovers that Bright Eyes had recently given birth and convinces Will to save the baby chimp's life by taking him home temporarily. Will's father Charles , who is suffering from Alzheimer's disease, names the chimp "Caesar". Will learns that Caesar has inherited his mother's high intelligence (the 112 virus passing to him in utero) and decides to raise him, working from home and observing his behavior in hopes that he can get the project restarted. Three years later, Will introduces Caesar to the redwood forest at Muir Woods National Monument. Meanwhile, with Charles' condition rapidly deteriorating, Will treats him with ALZ-112 and he is restored to better-than-original cognitive ability.
After five more years and upon seeing a dog on a leash like his own, Caesar openly questions his identity and Will tells him of his origins. Meanwhile, Charles's dementia returns as he has become resistant to the ALZ-112. Caesar witnesses a confrontation between confused Charles and neighbor Douglas Hunsiker and attacks Hunsiker. Caesar is then placed in a primate shelter where he is treated cruelly by the other chimps and the chief guard, Dodge Landon . Caesar learns how to unlock his cage, gaining free access to the common area. With the assistance of Buck, a gorilla, he confronts the sanctuary's alpha chimp and claims that position.
Will's boss Jacobs clears development of a more powerful, gaseous version of the viral drug (now called ALZ-113) when Will tells him it will not only heal brain disease but also improve intelligence in anyone. Will takes the drug home to try to save his father, but Charles declines, clutching Will's arm and shaking his head "no". Charles passes away overnight. Franklin is later exposed to the new drug 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 (after bribing the head of the shelter to release him), but the chimp refuses to go home with him. Instead, he escapes from the facility and returns to Will's house, where he takes canisters of the ALZ-113.
Returning to the facility, Caesar releases the gas, enhancing the intelligence of the other apes overnight. When Dodge attempts to get him back into his cage, Caesar shocks him by speaking for the first time, yelling "No!". Caesar then electrocutes the cattle prod-wielding Dodge by spraying him with water, unintentionally killing him. The apes flee the facility, release the remaining apes from Gen-Sys, and free the other apes from the San Francisco Zoo.
A battle ensues as the ape army fight their way past a police blockade on the Golden Gate Bridge to escape into the Redwood forest at Muir Woods. Buck sacrifices himself to save Caesar by jumping into the helicopter in which Jacobs is riding. The helicopter crashes onto the bridge, trapping Jacobs in the wreckage. Jacobs is then killed by Koba, an elder ape who had been a test subject all his life. As the apes find their way into the forest, Will arrives and warns Caesar that the humans will hunt them down, and begs him to return home. To Will's surprise, Caesar hugs him, symbolizing that he still loves Will. Caesar then speaks and says "Caesar is home". Will, realizing that this is indeed their last farewell, respects Caesar's wishes. The apes climb to the tops of the Redwoods. San Francisco, the city from which they escaped, can be seen in the distance.
Hunsiker—having been infected by Franklin—leaves his house for work as an airline pilot, arriving at San Francisco International Airport for his flight to Paris. His nose begins to drip blood onto the floor. A graphic traces the spread of the humanity-killing virus to Europe and then around the globe via international airline flight routes.
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