Plot
Athena-1, a space station owned by nefarious gene-manipulation company Energyne, is destroyed after a laboratory rat mutates and wreaks havoc. Kerry Atkins, the lone surviving crew member, manages to escape in an escape pod before the station implodes, along with a trio of pathogen canisters that Energyne CEO Claire Wyden ordered her to retrieve, but the pod disintegrates upon re-entry, killing Atkins. One canister is swallowed by an American crocodile named Lizzie in Everglades National Park and another lands in a Wyoming forest where a wolf named Ralph is exposed to the pathogen.
Primatologist Davis Okoye, a former Special Forces soldier and member of an anti-poaching unit, works at the San Diego Zoo Safari Park. He is friends with George, a rare leucistic western lowland gorilla that he rescued from poachers, and communicates with him via sign language. The third Energyne canister lands in George's habitat, exposing him to the pathogen.
As George grows considerably larger and more aggressive, Davis is contacted by genetic engineer Doctor Kate Caldwell, who explains that the pathogen was developed by Energyne to rewrite genes on a massive scale. She had hoped to advance research on CRISPR as a potential cure for diseases, but discovered Energyne's plans to use it as a biological weapon and was falsely incarcerated, during which her terminally ill brother passed away. George escapes from captivity and runs amok at the preserve. Davis calms him, but George is captured by a government team led by Agent Harvey Russell and put on a Boeing C-17 Globemaster III. Meanwhile, Claire and her brother Brett oversee a mercenary team's attempt to capture Ralph, but the entire team is killed.
Claire, resolving to capture Ralph and use George to cover up her plot, uses a massive transmitter atop the Willis Tower to lure the animals – engineered to respond aggressively to a certain radio frequency – to Chicago, unconcerned about the massive risk to civilian lives this poses. George reacts violently to the sound and crashes the plane, though Davis, Kate and Harvey parachute to safety. George survives the crash and joins Ralph as they make their way to Chicago, while Davis and Kate are aided by Harvey in stealing a UH-60 Black Hawk to pursue them.
Davis and Kate arrive to find George and Ralph tearing through Chicago as the military struggles to stop them; the situation worsens when Lizzie joins the duo. Planning to steal an antidote to turn the animals back to normal, Davis and Kate infiltrate Energyne's base of operations at the tower, but are caught by the Wydens as Claire reveals that the antidote only eliminates the animals' enhanced aggression rather than reversing all of the pathogen's effects. When George climbs to the top of the tower, Claire orders Davis to distract him while she attempts to escape with Kate at gunpoint. Kate slips a vial of the antidote into Claire's handbag and has George swallow her whole along with it, restoring his former personality. Harvey takes incriminating evidence from Brett and allows him to escape, but Brett is crushed to death by falling debris. As the damaged tower topples, Davis and Kate survive by crash-landing the nearby helicopter on the Federal Plaza.
Davis stays to help George defeat the other animals, while Kate and Harvey rush to prevent the military from deploying a GBU-43/B MOAB against them. During their confrontation, Davis tricks Ralph into attacking Lizzie, who decapitates him, and George ultimately manages to vanquish Lizzie by stabbing her in the eye with a broken rebar. With the threat neutralized, the airstrike is aborted and Davis is joined by his allies in rescuing civilians.
