Astronauts Taylor (Charlton Heston), Landon (Robert Gunner), Dodge (Jeff Burton) and Stewart (an uncredited Dianne Stanley) are in deep hibernation when their spaceship crash-lands in a lake on an unknown planet, after a 2006-year voyage at near-light speed (during which the crew ages only 18 months due to time dilation). The astronauts awaken to find their ship sinking and Stewart dead and her body desiccated due to an air leak in her suspended animation chamber. They use an inflatable raft to reach shore, but before departing the ship, Taylor notes that the current year is AD 3978. Once ashore Dodge performs a soil test and pronounces the soil incapable of sustaining life.
Despite this, as the three astronauts set off through a desert, they gradually encounter plant life. They find an oasis at the edge of the desert and decide to go swimming, ignoring strange and eerie scarecrow-like figures. While they are swimming, their clothes are stolen. Pursuing the thieves, the astronauts find their clothes torn to shreds, their supplies pillaged and the perpetrators — a group of mute, primitive humans dressed in torn clothes — contentedly raiding a cornfield.
Suddenly, clothed gorillas on horseback charge through the cornfield, brandishing firearms, snares, and nets. They capture some humans and kill the rest. While trying to flee, Dodge is killed, Landon is knocked unconscious, and Taylor is shot in the throat. The gorillas take Taylor to Ape City, where his life is saved after a blood transfusion by two chimpanzees and animal psychologist Zira (Kim Hunter) and surgeon Galen (Wright King). Taylor is housed in a cage with a girl whom he later calls Nova (Linda Harrison). Because of his throat wound he is unable to speak.
Taylor discovers that the various apes, who can talk and are in control, are in a strict caste system: gorillas are the police, military, hunters and workers; orangutans are administrators, politicians, lawyers and priests; and chimpanzees are intellectuals and scientists. Humans, who are believed by the apes to be unable to talk, are considered vermin and are hunted for sport, killed outright, enslaved, or used in scientific experiments.
Zira and her fiancé, Cornelius (Roddy McDowall), an archaeologist, take an interest in Taylor, whom Zira has named "Bright Eyes". Taylor attempts to communicate by writing in the dirt, but his writing is hidden by the Nova and Cornelius' boss, an orangutan named Dr. Zaius (Maurice Evans). Eventually, Taylor steals paper from Zira and uses it to write a message with his name to her. Zira and Cornelius become convinced that Taylor is intelligent, but upon learning of this, Dr. Zaius orders that Taylor be castrated.
Taylor manages to escape and during his flight through Ape City finds himself in a museum, where Dodge's stuffed corpse has been put on display (no other humans have his unique dark skin color). When Taylor is recaptured by gorillas, he overcomes his injured throat and angrily shouts, "Take your stinking paws off me, you damn dirty ape!"
A tribunal to determine Taylor's origins is convened by the president of the Assembly (James Whitmore), Dr. Zaius, and Dr. Maximus (Woodrow Parfrey). Dr. Honorious (James Daly) is the prosecutor. Taylor mentions his two comrades. The court produces Landon, who has been subjected to a lobotomy that has rendered him catatonic, and unable to speak.
After the tribunal, Dr. Zaius privately threatens to lobotomize Taylor if he does not tell the truth about where he came from. With help from Zira's socially-rebellious nephew Lucius (Lou Wagner), Zira and Cornelius free Taylor and Nova and take them to the Forbidden Zone, a taboo region outside Ape City that has been out of bounds for centuries by Ape law. A year earlier, Cornelius led an expedition into the Forbidden Zone that found a cave containing artifacts of an earlier non-simian (believed-to-be human) civilization. The group sets out for the cave to answer questions Taylor has about the evolution of the ape world and to prove he is not of that world.
Arriving at the cave, Cornelius is intercepted by Dr. Zaius and his soldiers. Taylor, now armed, holds them at bay, threatening to shoot them if necessary. Zaius agrees to enter the cave to disprove their theories and to avoid physical harm to Cornelius and Zira. Cornelius displays the remnants of a technologically advanced human society pre-dating simian history. Taylor identifies artifacts such as dentures, eyeglasses, a heart valve and, to the apes' astonishment, a talking children's doll. More soldiers appear and Lucius is overpowered, but Taylor again fends them off.
Dr. Zaius is held hostage so Taylor can escape, but admits to Taylor that he has always known that a human civilization existed long before apes ruled the planet, and that "the Forbidden Zone was once a paradise, [man] made a desert of it… ages ago!" Taylor is skeptical, and prepares to search for answers, but Dr. Zaius warns him that he may not like what he finds. Once Taylor and Nova have ridden off on horseback, Dr. Zaius has the gorillas lay explosives to seal off the cave and destroy the remaining evidence of the human society. He has Zira, Cornelius and Lucius charged with heresy.
Taylor and Nova, at last free, follow the shoreline and eventually discover the beach-covered remains of the Statue of Liberty, revealing that this "alien" planet is actually post-apocalyptic Earth. Taylor dismounts the horse, and falls to his knees in despair and anger, condemning humanity for destroying the world.