Caesar’s clan is at war with the human military faction known as Alpha-Omega. Caesar’s clan hides in Muir Woods, and Caesar offers the humans peace if the apes are left alone. This conflict has become further complicated as various apes, including the gorilla Red (a former follower of Koba), have joined Alpha-Omega after being disillusioned with Caesar’s leadership, in fear of retaliation from Caesar due to their betrayal. Learning that Alpha-Omega follows the leadership of a mysterious Colonel, Caesar makes plans to relocate the clan across the desert, not wanting to suffer any more ape casualties after Koba’s wrath on San Francisco. The night before their journey, Alpha-Omega launches an assault on the ape home and Caesar’s wife Cornelia and eldest son Blue Eyes are slaughtered by the Colonel, leaving only Caesar’s youngest son Cornelius alive.
Leaving Cornelius in the care of Lake, the mate of his deceased son, Caesar departs to confront the Colonel, accompanied only by Maurice, Luca and Rocket, while the other apes head for the desert. Confronting traitorous albino ape Winter, they learn that the Colonel has departed for a location called the “border”. During their journey, they are forced to kill a human living alone in an abandoned village, but when they discover his young daughter, apparently unable to speak, Maurice insists that they take her with them. Further along, they discover that some Alpha-Omega soldiers that have been shot and abandoned. Their examination of a survivor reveals that he, like the girl, cannot speak. In an abandoned souvenir shop, the group meets Bad Ape, an ape hermit who lived in the Sierra Zoo before he was exposed to the Simian Flu virus. Bad Ape is able to direct them to the border, a former weapons depot that was turned into a containment facility when the virus began to spread.
When the group arrives at the border facility, Luca is killed by an Alpha-Omega patrol, prompting Caesar to enter the facility alone. However, he is captured shortly after learning that the rest of his ape family have been caught by the Colonel. Witnessing his fellow apes being forced to build a wall, Caesar confronts the Colonel, who reveals that the Simian Flu virus has evolved further and is now causing some surviving humans to become mute and regress back to a primitive mentality. The Colonel is barricading himself into the facility to fend off rival military forces coming to execute him, as he favors killing any infected humans – including his own son – while others believe that a cure is still possible.
While Caesar is tortured with starvation, the mute girl, whom Maurice names Nova, sneaks into the facility to give him food and water, although Rocket is forced to allow himself to be captured to create a distraction so that Nova can escape. Together, Caesar and Rocket are able to work out a means of accessing the ape cage via an underground tunnel that leads out of the facility, with Bad Ape and Maurice digging their way into the cage. After rescuing the children, Caesar sends his followers away while he confronts the Colonel, but the facility is subsequently attacked by the external military forces. When Caesar reaches the Colonel, he realizes that the Colonel has succumbed to the infection and is regressing to a primitive state. Caesar ultimately spares the Colonel, who takes his own life rather than become a primitive. In a massive battle among Caesar’s apes, Alpha-Omega and the rival militants, Red redeems and sacrifices himself by saving Caesar’s life, helping to destroy the facility’s fuel supplies. As the apes fall in numbers, an oncoming avalanche arrives, and wipes out the remaining Alpha-Omega soldiers, as well as the opposing militant forces, while the apes and Nova retreat to the safety of the trees.
Departing the facility, the remaining apes cross the desert and find a park that is rich in natural resources. Caesar reveals to Maurice that he was mortally wounded during the escape, and that he is going to die. Before Caesar dies, Maurice assures Caesar that Cornelius will know what his father did and what he stood for.