Noticing many jungle animals behaving in an unnatural manner, adventurer Jungle Jim, Johnny Weissmüller, sends a handful of specimens to a laboratory for testing to uncover the cause. This unsettling pattern signals a far darker plot lurking beneath the jungle’s surface.
It is revealed that the diabolical scientist Doctor Andrews, Nestor Paiva, is behind the scheme. Andrews is intent on formulating a deadly drug that would make any creature injected with it succumb in seconds, turning the wild into a possible tool of catastrophic control.
Jim, unaware of Andrews' plans, spots him near the Canyon of the Man Ape. The jungle explorer urges him to depart quickly, as rumors tell of a fearsome creature—the Man Ape, Max Palmer—roaming the canyon’s grounds, a half-man and half-ape menace that could spell disaster for anyone who gets too close.
Andrews does not heed the warning, and his jungle laboratory is obliterated by the legendary “Killer Ape.” The act marks a turning point, as the natural world fights back against the tampering of science.
Jungle Jim later meets Mahura, Paul Marion, leader of the tribal Wazuli clan. Jim warns him of the Killer Ape, but Mahura wants to see the threat for himself to believe it. He ventures into the canyon and comes face to face with the enraged monster.
Jim comes to Mahura's aid but is knocked out cold by the beast. The Killer Ape proceeds to kill the tribal chief, a shocking blow that ignites fear and suspicion among the clan. Shari, Carol Thurston, Mahura's daughter, and Ramada, Burt Wenland, Mahura's spouse, both accuse Jim of murdering Mahura. When Jim vehemently denies it, a heated quarrel erupts. Jim sneaks away but is chased by Shari. Just then, the Killer Ape reappears and tries to kill Shari, only to be scared off by Jim.
Meanwhile, Ramada has learned of Andrews' scheme and decides not to let him harm the jungle animals anymore. Ireful, Andrews orders his men to kidnap both Ramada and a tribal elder. Jungle Jim also gets caught while trying to rescue the captured duo.
When the Killer Ape re-bags Shari and returns to the canyon, the captives are taken along as well. Jim's pet chimpanzee Tamba ropes in his fellow ape friends, and together they storm into Andrews' retreat. The captured are freed, and the Killer Ape, enraged, massacres all of Andrews' henchmen and lets the doctor be mauled to death by a panther. It then shifts its focus when it sees Shari, and, attempting to drag her away, its plans are permanently halted by Jim, who burns it alive.
In the aftermath, Jungle Jim is awarded a medal for ridding the jungle of the Killer Ape, a testament to the delicate balance between discovery and danger that governs life in the wild. The tale leaves a message about power, responsibility, and the resilience of those who stand against reckless experimentation.