Following the events of Planet of the Apes, time-displaced astronaut Taylor and the mute Nova ride horseback through the desert of the Forbidden Zone in search of a new life far away from Ape City. Without warning, fire shoots up from the ground and deep chasms open. Confused by the strange phenomenon, Taylor investigates a cliff wall and disappears through it before Nova’s eyes. The phenomenon disappears, leaving Nova alone.
Elsewhere in the Forbidden Zone, a second Earth spaceship has crash landed after being sent to search for Taylor and his crew. Brent and his Skipper are the only survivors, though the Skipper dies shortly after crashing. Brent, while noting he is in the year 3955, assumes he has travelled to another planet. After burying his Skipper, he encounters Nova and notices she is wearing Taylor’s dog tags. Hoping Taylor is still alive, he rides with her to Ape City, where he is shocked to discover the simian civilization. He observes the gorilla General Ursus leading a rally for the apes to conquer the Forbidden Zone and use it as a potential food source, against the objections of the orangutan Dr. Zaius. Brent is wounded by a gorilla soldier and taken by Nova to the home of the chimpanzees Cornelius and Zira, who treat his wound and tell him of their time with Taylor. The humans hide when Dr. Zaius arrives and announces that he will accompany Ursus on the invasion of the Forbidden Zone.
Attempting to flee the city, Brent and Nova are captured by gorillas. Ursus orders they be used for target practice, but Zira helps them escape. They hide in a cave which Brent soon discovers is the ruins of the Queensboro Plaza station of the New York City Subway, realizing he traveled through time to Earth’s post-apocalyptic future. After following a humming sound deeper into the tunnels, Brent begins to hear voices telling him to kill Nova. Entering the remains of St. Patrick’s Cathedral, he finds a population of telepathic humans who worship an ancient nuclear bomb.
Brent and Nova are captured and telepathically interrogated by the telepaths’ leadership under Mendez. They explain themselves to be the descendants of humans who survived nuclear holocaust and mutated over generations. While claiming to be a peaceful society despite using mind-control and illusion on their enemies, the mutants force Brent into revealing the apes’ march on the Forbidden Zone; but their attempts to repel the invaders with illusions of fire and other horrors ultimately fail when Zaius sees through it. With the apes closing in, the telepaths plan to detonate their “Divine Bomb” as a last resort, holding a religious ritual during which they remove their human-skinned masks to reveal their malformed skinless appearance from generations of radiation exposure.
Brent is separated from Nova and taken to a cell where he finds Taylor. The mutant Ongaro, explaining that they cannot let them leave the city alive, uses his telepathic powers to force Brent and Taylor to fight each other. Nova escapes her guard and runs to the cell, screaming her first word: “Taylor!” This breaks Ongaro’s concentration, freeing Brent and Taylor from his control long enough for them to overpower and kill the mutant. Brent describes the bomb the mutants worship to have Greek letters Alpha and Omega on its casing, Taylor recognizing it as a “doomsday bomb” capable of destroying the entire planet.
The apes invade the subterranean city, making their way to the cathedral; many of the mutants are either captured, killed, or found to have committed suicide. After Nova is killed in the midst of the chaos, Taylor and Brent reach the cathedral as Méndez is shot dead after raising the bomb into activation position. The humans attempt to stop Ursus from accidentally setting off the weapon, but Taylor is shot as his pleas to Zaius fall on deaf ears. When Brent is gunned down after killing Ursus, the mortally wounded Taylor collapses while bringing his hand down on the activation switch and triggering the bomb. The scene whites out, and voiceover narration states: “In one of the countless billions of galaxies in the universe lies a medium-sized star, and one of its satellites, a green and insignificant planet, is now dead”.