After a voiceover of Cornelius repeating the Humans Are the Real Monsters litany from the previous film, we watch as Taylor and Nova encounter the ruined Statue of Liberty essentially repeating the last few minutes of the previous film. After recovering from his near breakdown, Taylor and Nova ride off towards the other jungle.
We cut to somewhere in the wilderness, where a ship very much like the one from the first film has crashed. A male astronaut, remarkably similar to Taylor in looks, stumbles out of the wreck, holding supplies and attending to an older man, lying wounded on a nearby blanket. As the two men converse, we learn the Taylor-look-alike is named Brent, and he and his "Skipper" were sent from Earth to try and rescue Taylor and his crew, and they have fallen through the same strange phenomena that they theorize has stranded Taylor. The old man dies and is buried by Brent, who is wondering where to start, when up rides a horse, on which is mounted Nova.
Brent tries to communicate with the mute girl, especially when he sees she is wearing Taylor's dogtags. Nova manages to understand him sufficiently to realise he is asking about Taylor, recalling that Taylor vanished some time ago after they were beset with mysterious phenomena that culminated in Taylor falling through a solid rock wall. Unable to communicate this to Brent, Nova finally takes his frustrated comments of "finding someone to talk to" as an excuse to lead him to Ape City.
Hidden in the wilderness, Brent and Nova watch as a great council of apes is held, a gorilla general named Ursus coaxing the apes to approve a plan of his to invade and conquer the Forbidden Zone by playing on their fears. Cornelius and Zira are watching the whole affair, but Zira is quite obviously disgusted with what is going on. Finally, the council breaks up, with Ursus having been given permission to launch his campaign.
In private, Ursus and Dr. Zaius talk about the Forbidden Zone, revealing the apes truly are in crisis, as famine is looming and they desperately need new croplands to grow food in. Furthermore, a dozen scouts from the Army have already been sent out to explore the Forbidden Zone; the first eleven vanished and the last one returned ranting about strange visions, evidently driven out of his mind.
Meanwhile, Cornelius and Zira return to their home, privately arguing about this latest scheme by the gorillas and their general barbarity. They are surprised when Brent and Nova emerge from hiding in their home, the mute native having led the astronaut there due to remembering her and Taylor's experiences with the couple. They explain their connection to Nova and Taylor to Brent, telling him where they saw him last and showing him a map to the Forbidden Zone. The two humans are forced to hide when Dr. Zaius drops in for a surprise visit, explaining to the two chimps that he must accompany General Ursus' expedition and he wants to leave them in charge while he's gone.
Once Zaius has left, Brent and Nova try to flee Ape City, but are caught by gorilla soldiers. At the human center, Zira tries to subtly save them, but the gorillas refuse, telling her that these two are to be taken for target practice. Zira still manages to steal the key and unlock their cage as they are carted away to their death.
Once safely out in the wilderness, Brent escapes the cage and manages to right the gorilla driver off, allowing him and Nova to steal the cart's horses and ride away towards the Forbidden Zone. More gorillas pursue them, while back in Ape City, Ursus and Zaius brutally disrupt and imprison a peaceful chimpanzee anti-war protest before continuing on to the Forbidden Zone.
In their efforts to hide from the gorillas, Brent and Nova seek refuge in a cave that leads to ancient ruins of a New York subway tunnel; this clues Brent in to the same realisation as Taylor in the previous film's ending. A strange sound lures them deeper into the ruins, culminating in them finding a bizarre chamber. Their explorations are interrupted when an inexplicable madness comes over Brent, causing him to attack Nova and almost drown her. He manages to fight it off and stumbles through a set of doors, where he finds himself in an eerie, church-like setting, confronted with a strange figure in a white robe. Brent tries to communicate with him, but instead finds himself captured and imprisoned by the strange people.
The leaders of the strange humanoids pressure Brent to tell them what he knows of the apes' plans, using their strange Psychic Powers to torture him into compliance and refusing to listen when he protests he doesn't really know anything. Finally, they try to make him kill Nova again, whereupon he breaks down and admits the apes plan to attack the city.
Brent watches as the humans perform a religious ceremony, revealing they worship a surviving atomic bomb from before whatever it was that led to the apes dominating... as well as displaying that they are hideously deformed. While Nova is taken elsewhere, Brent is thrown into a cage with Taylor. When the two try to call the mutant standing guard over them on his hypocrisy, he sets the two to fighting. With the surprise appearance of Nova, though, they manage to fight it off and kill him, then start trying to free themselves. As they talk, Taylor confirms that the bomb the mutants worship is the "Alpha-Omega Bomb", a cobalt bomb that will utterly destroy the Earth if detonated.
At roughly the same time, the ape army is invading the Forbidden Zone. The mutants' illusions stymies them for several moments before their attempts to use a bleeding statue of their sacred Lawgiver to frighten them off spurs Dr. Zaius into proving the illusions are just that. Confidence restored, the apes charge onwards, finding their way into the mutants lair and beginning to slaughter everyone in their path.
Brent, Taylor and Nova finally escape, but too late; the apes are already there and Nova is fatally shot before Taylor can kill the gorilla attacking them. Despairing, but determined to stop the apes from inadvertently destroying them all, the two astronauts press on to the chamber of the "Holy Bomb". There, they witness the last mutant priest almost finish activating the bomb before being gunned down... and then General Ursus orders his gorillas to start tampering with the bomb. Brent and Taylor try to intervene to stop them from dooming them all, but Brent is killed and Taylor mortally wounded. He pleads with Dr. Zaius to help him stop the destruction, but Zaius refuses to help a human, citing how all humans are evil. Spitting curses, Taylor falls forward, dead... And pushes down the last of the activation switches.
A voiceover then describes how an insignificant blue-green planet has ceased to exist.
