Apes are captured and sent to Gen Sys, where their eyes have been transformed into green eyes. Gen Sys is a genetic therapy pharmaceutical company. A female ape, labeled No. 9 and nicknamed "Bright Eyes" by the staff, has been administered the medicine ALZ 112 and has made significant progress. She is more friendly and peaceful than other apes, and she completed the Towers of Hanoi puzzle in 20 moves, close to a perfect score of 15. Will Rodman talks to his employer, Steve Jacobs, and persuades him that he has data that allows them to proceed with human trials for the medicine.
The following day, Rodman and Jacobs appear in the conference room in front of the Gen Sys board of directors. Will adds that the new medicine induces neurogenesis, the formation of new brain cells (which does not normally occur after birth), and may treat a variety of degenerative brain conditions, including Parkinson's and Alzheimer's. The only side effect is that the medicine causes a green shine in the individual's eyes.
Back in the lab, Robert Franklin, the senior ape caretaker, has difficulty getting Bright Eyes out of her cage. She is violent towards Robert and the other aides. They try to coax her out of the cage with orange soda, but when they try to catch her with a lasso pole, she goes "ape" and runs wild through the building. The chase ends when she crashes through the conference room's glass window, and the building's security personnel murder her.
Jacobs declares the drug experiment 'dead,' fearing that what they experienced with Bright Eyes was a drug-induced violent side effect. Will tries to persuade Jacobs to change his mind but refuses, claiming he wants the remaining test apes 'put down.'
Robert returns to the lab and shows Will a newborn ape hidden in Bright Eyes' cell. This explains why their presumption was incorrect: Bright Eyes was not responding violently because of the drug, but to defend her infant. Robert did not have the heart to put down the baby, so he delegated the responsibility to Will. Unwilling to do so, he decides to bring the infant home.
Will comes home and lives with his father, Charles. Charles has Alzheimer's and requires care from a nurse when Will is not present. Will introduces the newborn ape to Charles, who quickly takes a fancy to it. Charles jokingly refers to the baby as Caesar.
Caesar quickly makes extraordinary progress, being able to feed himself after only two days; he appears to have contracted the virus-based ALZ 112 from his mother. His "temporary" residency with Will lasts three years, and Will makes up a place for him in the attic. By 18 months, Caesar could sign up to 24 words. By the age of two, Caesar was finishing puzzles and models designed for kids aged eight and up. At the age of three, Caesar continues to demonstrate cognitive abilities that are much above those of a human equivalent. He completed the Lucas Towers in 15 moves, earning a perfect score. He also plays chess rather well. Though apelike in some aspects, the now-half-grown Caesar is a treasured family member with considerable intelligence, articulating complex thoughts through sign language.
While Caesar's mental development is improving, Charles' Alzheimer's disease worsens, and he disagrees with his nurse. Will takes a significant risk by stealing ALZ 112 from Gen Sys. He administers a dose to Charles, and the next day, Will discovers his father playing the piano flawlessly.
Meanwhile, Caesar has become enamored with watching the neighbors play outdoors and escapes through the window into their neighbor's backyard. However, Caesar's appearance alarmed the neighbor's daughter, and her father, Hunsiker, attacked him angrily. Will and Charles successfully rescue Caesar, but not before Hunsiker injures him. Will sneaks Caesar into the zoo for treatment. Caroline Aranha, a veterinarian, treats Caesar there. Caroline is captivated by Caesar's knowledge of sign language; he even suggests that Will and Caroline go out to supper using sign language.
To quell Caesar's wanderlust, they transport him across the Golden Gate Bridge to a redwood forest for outdoor play. When Caesar arrives at the woodland, he does not leave Will but instead makes a supplication motion by extending his arm and palm up to ask for permission to play. Will permits him, and Caesar goes to the trees. Caroline has joined the Rodman family five years later, and Caesar has grown. Will has even begun dressing in a shirt and trousers. During a walk to the wilderness, Caesar is aggressively barked at by a dog, and he responds with a primal howl that drives it away. Will senses Caesar's sadness and confusion over who he is. So they drive by Gen-Sys, and Will tells Caesar about the medicine that increased his intelligence, as well as the loss of his mother.
Charles' condition has deteriorated over the last five years following receiving ALZ 112. Will believes that his immune system has created antibodies and that a more aggressive virus is required. Back at home, Charles becomes disoriented and goes outdoors, into their neighbor's automobile. He tries to drive it but damages it. Hunsiker (the same neighbor who attacked Caesar) yanks Charles from the automobile; in his deranged state, Charles is unable to express his reasons for being there. Caesar watches from his attic window, and when he sees the neighbor cursing and aggressively pushing Charles, he runs out of the house. He attacks Hunsiker, knocking him to the ground, jumping on him, beating him, and eventually biting off a finger. Charles recognizes Caesar and exclaims, "Caesar, no!" Caesar backs off and approaches Charles. Animal control transports Caesar (by court order) to a primate "sanctuary" following the incident. Will and Caroline walk him in and say their goodbyes.
During Caesar's first days in the sanctuary, he finds it difficult. It is run by John Landon, with animal care overseen by his short-tempered and aggressive son Dodge Landon and a timid man named Rodney. The court order had not yet been entered into the system, so Will was forced to wait for the appeal for at least 90 days. Will takes a risk by going to Jacobs, disclosing his secret experiment with his father, and explaining that the medicine not only heals brain damage but also makes people clever. He claims he has altered the virus and requires Jacobs to allow new animal tests.
When Caesar flings his food at Dodge and laughs, the young guy responds violently by turning on a fire hose, sending Caesar to cower in the corner of his cage. Caesar misses his home in the attic. The sanctuary sends 12 apes to Gen Sys to test the latest version of ALZ 112, which is called ALZ 113. Will is once again in charge of the testing, and his first subject is a pretty frazzled ape named Koba. Koba is strapped down and administered the new medication via a breathing mask. However, Koba resists, and the hose falls off the machine. Almost everyone in the lab wears a breathing mask, but unfortunately, Robert gets accidentally exposed.
When Caesar and the other animals are released into the main play area, they meet the group's dominant male, an ape named Rocket. Rocket rips off Caesar's shirt and beats him. Caesar also notices a gorilla named Buck in a locked cage. Dodge shoots Rocket and Caesar with an anesthetic injection to stop the fight. The intelligence results on Koba are astounding. They notice no negative effects. They discovered that apes have an extremely robust immune system. Meanwhile, Robert Franklin has been experiencing virus-related side effects such as sneezing, which causes blood droplets to emerge from his sinuses
An orangutan across from Caesar communicates in sign language. Caesar quietly begins to converse with Maurice, an orangutan. In the words of Maurice, "Humans do not like smart apes." At the same time, men carry an ape to GenSys. Will visits Caesar and discovers that they treat apes poorly. Caesar again requests that he take him home. But Will is compelled to say no. Caesar becomes enraged because he is unable to comprehend the situation.
Dodge eventually leads some of his buddies into the sanctuary's cage section, where Caesar steals a pocket knife from one of the guests. By releasing him, Caesar befriends Buck, the giant gorilla in the yard who is never allowed out of his cage. He then releases Rocket, who ventures into the garden. Caesar attacks him with a steel gasoline can. Rocket is prepared to fight, but he realizes that Buck is loyal to Caesar and will protect him, so he surrenders. Caesar is now the alpha male.
That night, Will brings some ALZ 113 home to treat his father. Charles refuses therapy and dies that night in his sleep. After Will and Caroline finish packing away Charles' remaining items, Will notices a photograph of him and Caesar.
Will returns to work and discovers that Jacobs has shamelessly and carelessly pushed the research timeline forward. While Jacobs is primarily concerned with economic earnings, the most pressing issue is how the newer ALZ 113 would affect humans. Will quits Gen-Sys as Jacobs refuses to listen to his concerns. Robert goes to Will's house to talk to him, but Will is not present, and Will's irritable neighbor, Hunsiker, confronts Robert. Robert, startled, sneezes on him.
Will returns to the monkey sanctuary and tries to bribe John Landon into letting him keep Caesar. John is eager to do so, but when Will persuades Caesar to accompany him, he declines to accompany him.
Caesar then lets Rocket out of the cage and allows him to distribute stolen cookies (from Dodge) to each ape, bringing unity to the community. Maurice asks Caesar, "Why Rocket Cookies?" Caesar responds, "Apes alone weak; "Apes together strong." Maurice says, "Apes stupid," and walks away. Observing Rodney, Caesar has also discovered a walkway and controls for the windowed enclosure at the top of the play area.
That nightfall, Caesar bursts out through the window he discovered and returns home. He grabs ALZ 113 from Rodman's refrigerator and delivers it to the apes at the preserve. The next day, Caesar checks all the apes to see if their eyes have changed green color. The same day, John Landon witnessed the apes holding a conference. The apes scatter and play it off. Landon dismisses it as odd. Later on, a woman in Robert's building discovers his death.
That night, the apes return to their cages, but Caesar refuses, confronting and 'defeating' Dodge in the yard. When grabbed, Dodge exclaims, "Take your stinking paws off me, you dirty ape!" Caesar talks (audibly) for the first time, exclaiming "NO!" The second caretaker, a witness, rushes into the cage area, attempting to save Dodge, who is now comatose.
The apes assault him, but Caesar calls them off and, as a gesture of mercy, places him in Caesar's cage. Dodge tries to flee and is slain. (He's holding a cattle prod, and Caesar hits him with the fire hose.) And apes escape from there. Will calls Caesar in the morning, but there is no answer.
Meanwhile, the apes make their way across town. Caesar separates them into two groups. Buck goes with one group to the zoo to free the apes, while Caesar leads the other group to Gen Sys. Will, driving there to investigate, discovers the facilities destroyed, the apes missing, and the ALZ 113 canisters open in the cage sections. He chooses to sound the alarm. Rodney tells Will that his Ape spoke.
The police are called in. John Landon, Will, and the police examine the camera footage and determine what occurred. Apes enter the facility centers and release all the other apes caged there, including Koba. Jacobs, who has just arrived at work, learns about the apes’ escape, Robert’s death, and the reason behind it.
He discovers that Caesar and the other apes have taken over the building, freeing the 12 ALZ 113 test subjects.
Jacobs boards a police helicopter. Caesar and Buck's groups join forces, numbering between 50 and 60 chimps, orangutans, and gorillas. However, the apes appear to be deliberately preventing the deaths of the humans they encounter. They also fight the police, who target them. Will and Caroline had heard about the rampage, and after learning that the apes are on their way to the Golden Gate Bridge, they believe Caesar is leading them to the redwood grove. The officers are waiting on the bridge to fire on the apes, but Caesar once again separates his forces. One group climbs the suspension cables, while another swings from the structure's underside to bypass the blockage.
In the helicopter, Jacobs notices Caesar and tells them to shoot him, assuming that Caesar's death will deter the others. When the men shoot apes, apes become more angry and fight back aggressively. However, when the aircraft approaches the bridge, Buck climbs upon it, bringing it down at the expense of his own life. The loss of his colleague saddens Caesar and he soon discovers the helicopter's remains clinging to the side of the bridge, with Jacobs crying for help. Instead, Caesar looks away, and Koba pushes the chopper off, killing Jacobs on impact with the ocean.
The apes move into the jungle. Will and Caroline, in the meantime, have made their way across the bridge. Will steals a police car and escapes into the forest. He calls Caesar's name but is confronted by one of his followers. However, Caesar soon emerges, and the others retreat. Will tries to reconcile with his pal, promising to protect him if Caesar comes home with him. Caesar surprises Will by embracing him tight and whispering, "Caesar is home." Stunned, Will agrees with him and watches Caesar and a few other apes climb into the trees to observe the forest and the world beyond.
In the aftermath, we witness Will's neighbor Hunsiker report for duty as a pilot at San Francisco International Airport. As he walks towards his jet, he notices that he is bleeding from his nose. As the camera pans up, we observe digital boards blinking to various destinations, indicating that these locations will soon be infected with ALZ 113, sealing humanity's fate.
