Following the events in "Beneath the Planet of the Apes", Cornelius and Zira flee back through time to 20th Century Los Angeles, where they face persecution similar to what Taylor suffered in the future, and discover the origins of the stream of events that will shape their world.

In 1973, military personnel rush to a beach in Southern California when a spacecraft is found floating in the ocean. After the craft is reeled in and its three occupants, wearing helmets and spacesuits, disembark, the waiting officers salute them. Everyone is astonished, however, when the astronauts remove their helmets and reveal that they are human-sized chimpanzees who stand upright. After hustling the chimps to a military base, the soldiers are instructed to bring the apes to the Los Angeles Zoo infirmary to be studied in secrecy. In the morning, at the zoo, the chimps are put into a cage next to a depressed gorilla, and as they wait, the chimps¿archaeologist Cornelius, his psychiatrist wife Zira and scientist Milo¿who are from Earth's future and can talk, discuss their predicament. Milo theorizes that they were thrust backward through time to Earth's past, even though they saw the Earth destroyed by a nuclear bomb, the result of a war in their own time of 3955. Milo advises his compatriots to remain silent, as apes of 1973 cannot speak. When zoologists Lewis Dixon and Stephanie "Stevie" Branton enter, the chimps act intelligently but remain quiet, and Zira easily masters the psychological tests given to her. When Stevie wonders why Zira does not grasp a banana placed before her, Zira blurts out that she loathes bananas. Overcome at hearing an ape talk, the zoologists hurriedly exit. Milo, Cornelius and Zira then quarrel over Zira's actions, and as their tempers escalate, the enraged gorilla in the adjoining cage strangles Milo to death. The sympathetic Lewis and Stevie console Cornelius and Zira, making friends with them, and caution them to reveal their ability to speak only to "the right people." Later that afternoon, the President of the United States tells a group of advisors about the arrival of the apes in a long-missing U.S. spaceship, and orders the formation of a presidential commission of inquiry. The following day, Dr. Otto Hasslein, the president's senior science advisor, joins the committee as Lewis presents Zira and Cornelius. When the two chimps speak, the committee and audience are both thrilled and horrified. Upon questioning, Cornelius and Zira reveal that where they come from, apes speak while humans are dumb, and Zira barely stops herself from saying that she dissects humans, instead correcting herself to say that she examines them. The pair skirts the question of where they come from, instead pleading that they are peaceful creatures and asking to be unchained. A standing ovation from the audience prompts the removal of their bonds, and the hearing is adjourned. In a nearby room, Zira insists to Cornelius that they must tell Lewis and Stevie the truth, and so reveals that not only are they from Earth's future, they knew Col. Taylor, the human astronaut who originally piloted the craft that they salvaged and used. They state that they helped Taylor evade the militaristic gorillas, who hunted humans for sport, and that as a zoologist herself, Zira conducted experiments on living humans. Although Lewis and Stevie are shocked, they admit that what Zira did is no different than what they currently do to "dumb" beasts. The next day, Cornelius and Zira are ensconced at the Beverly Wilshire Hotel, then outfitted in the latest human fashions. At a party that night, Lewis introduces Zira to champagne, which he calls "grape juice plus." The following day, Zira speaks about women's rights while Lewis takes Cornelius to a prizefight, which Cornelius calls "beastly." Later that afternoon, Hasslein takes Zira to the Natural History Museum, where she faints upon seeing a stuffed gorilla. Hasslein assumes that her fainting spell was caused by shock, but the pragmatic Zira informs him that she is pregnant. Upon taking her back to the hotel, Hasslein deliberately gets Zira drunk on grape juice plus and secretly records her as she answers his questions about seeing the destruction of the Earth. She also reveals that the war was started by the gorillas, who were fighting an enemy never seen by the pacifist chimpanzees. Hasslein plays the recording for the level-headed president, who demands concrete proof of the apes' ill intentions before destroying them. The president reminds Hasslein that Herod also attempted to slaughter the innocents, and questions him about whether they have the right to alter the future. Hasslein insists that Cornelius and Zira's baby could be the beginning of the race of speaking apes, and persuades the president to allow him to use CIA agents to interrogate the apes. Lewis and Stevie accompany Cornelius and Zira to a secret military camp, where Cornelius caustically states that humans' downfall comes from their habit of murdering one another rather than any aggression from the apes. Assuring Cornelius that the session is a fact-finding inquiry rather than "an interracial hassle," Hasslein orders Cornelius sequestered while Lewis is forced to give Zira an injection of truth serum. While drugged, Zira reveals that she often experimented on live humans, even giving them lobotomies, and that she knew Taylor. When Zira's revelations are relayed to the commission, they agree that while there is not conclusive evidence of the apes' hostility, Zira's pregnancy must be terminated, after which both apes will be sterilized. Back at the camp, Cornelius is fuming about Zira's treatment when an orderly offends him and Cornelius slams the orderly's tray into his face. Unaware that he has accidentally killed the youth, Cornelius leads Zira away and they escape. In the forest, however, Zira's labor begins, and Cornelius decides to return for help. As he creeps along the road, Cornelius is horrified to hear a soldier tell Stevie that the orderly was murdered. Stevie, who has been informed by Lewis of the committee's decree, believes Cornelius when he tells her that the killing was accidental, and takes him and Zira to a circus run by Armando, an animal lover who agrees to shelter the apes. As Zira cries in pain, Heloise, the circus' chimpanzee, holds up her own new baby, Salome, "to show an expectant mother what to expect," according to Armando. Soon Zira gives birth to a healthy boy, whom she and Cornelius name Milo. Later, Hasslein, suspecting that apes would hide among other apes, orders a search of all menageries and circuses. Lewis alerts Armando, who had hoped to take Cornelius, Zira and Milo to the circus' winter quarters in a month's time. Before they leave, Zira enters Heloise's cage to say goodbye to her and Salome. Later that night, Lewis and Stevie take the chimps to a deserted area and, giving them provisions, instruct them to hide in a deserted oil tanker at a nearby harbor until they can return to Armando. Giving their human friends a kiss goodbye, Cornelius and Zira begin their trek, but during their journey, Zira cannot carry both Milo and her suitcase, and so dumps the suitcase in an oil derrick. The suitcase is discovered the next morning, and when Hasslein spots the harbor nearby, he drives there to investigate. As Hasslein searches the tanker, the military and police arrive, followed by Lewis and Stevie. The two zoologists watch in horror as Hasslein shoots and mortally wounds Zira, then shoots baby Milo multiple times. Cornelius uses the pistol given to him by Lewis to kill Hasslein before he himself is brought down by a hail of bullets. The distraught Lewis then comforts Stevie as they watch Zira stagger to the baby and toss its body into the ocean, then crawl to Cornelius before dying. A month later, as Armando's circus prepares to move south, Armando goes to the cage of a baby chimp, which wears the St. Francis of Assisi medal that he had given to Milo. Petting the baby's hand, Armando comforts him by saying, "Intelligent creature, but then, so were your mother and father." After Armando walks away, the young chimp begins to cry out, "Mama, mama."