Will Rodman (James Franco) is a San Francisco scientist who has been trying to develop a cure for Alzheimer's disease by testing a genetically engineered retrovirus on chimpanzees. The virus mutates the chimpanzees, giving them a human level of intelligence. One of his test subjects, a female chimpanzee, goes on a rampage because she believes her baby, to whom she secretly gave birth, is threatened. She is killed after disrupting a board meeting. Will's boss Steven Jacobs (David Oyelowo) orders subordinate Robert Franklin (Tyler Labine) to put all the test chimpanzees down, but he cannot bring himself to kill the chimpanzee's baby, and instead gives him to Will, who names him Caesar (Andy Serkis) and raises him in his house. Caesar has inherited his mother's high intelligence, and learns quickly.
Three years later, Will gives a sample of his cure to his father, Charles (John Lithgow), who is suffering from Alzheimer's disease. At first, his father improves but, five years later, his body's immune system fights off the virus and his dementia returns. In his dementia, Charles gets into his neighbor's car and damages it, angering the neighbor (David Hewlett). As he threatens Charles and pushes him down, the onlooking Caesar attacks him. After the incident, Caesar is forced to leave Will's house and is held in a San Bruno primate facility run by John Landon (Brian Cox). The apes are treated cruelly by Landon's son Dodge (Tom Felton) who works as a guard there. Caesar is initially treated poorly by both the staff and the other apes. When Dodge brings his friends into the facility, one of them gets too close to Caesar's cage and is grabbed by Caesar, who steals his pocket knife, later using it to escape his cell. Caesar then frees a gorilla named Buck and, with his help, gains dominance over the other apes.
Meanwhile, Will creates a more powerful form of the virus to further treat his father and new tests on chimpanzees begin. Testing on a bonobo named Koba reveals that it strengthens the intelligence of the apes even further. However, it is fatal to humans, unbeknownst to the scientists. Franklin is exposed to the new virus and begins sneezing out blood. He accidentally sneezes on Will's neighbor, and is later found dead in his apartment. Will attempts to warn Jacobs against further testing, but when Jacobs plans to continue it, Will quits his job.
Caesar eventually escapes from the primate facility and travels to Will's house, where he steals canisters of the new virus and releases it throughout the cage area, enhancing the intelligence of his fellow apes. He beats Dodge down and, after showing his first capability of speech by shouting "No!" at him, electrocutes him by spraying him with a hose while his stun stick is activated. The apes at the facility escape into the city, releasing the remaining apes from Will's former place of work and from San Francisco Zoo.
The apes then force their way past a police blockade of the Golden Gate Bridge meant to stop them from crossing. Jacobs arrives in a helicopter and one of his crewmen begins gunning down apes. Buck sacrifices himself to take down the helicopter, which crashes on the bridge, killing everyone inside except Jacobs. He begs for help, but his helicopter is pushed down into the bay below by Koba. The apes make it into the Muir Woods National Monument forest. Will arrives at the forest and is attacked by Koba, but Caesar stops him from harming Will. Will warns Caesar that humans are strong, but tells him that he can protect him if he returns home. Caesar, now capable of speech, tells him that "Caesar is home" in the redwood forest. Meanwhile, the virus responsible for raising the apes' intelligence has started a global pandemic among humans.
