At the beginning of the film, a woman attempts to avoid a rat that had been mutated by the pathogen, becoming aggressive and bloodthirsty as a result. However, three of the canisters containing the pathogen are released onto the Earth after the woman's escape pod explodes. One of the canisters lands into the gorilla habitat, which leads to George, a rare albino gorilla, accidentally becoming infected by the pathogen, which causes him to grow rapidly as well as to become extremely vicious. The remaining two canisters infect two other animals - a crocodile and a wolf - causing them to become gargantuan hybrids. Davis, a primatologist and the leader of an anti-poaching unit, is contacted by Kate who tells him that she could find a way to cure George. However, they are both captured by a government team lead by Agent Russell. When Claire is informed about George, she devices a plan where the giant animals are lured to Chicago by a massive transmitter that generates certain sound frequencies so that they could be dissected.
However, this could end up leveling the city, killing dozens of citizens in the process, but Claire expresses no concern over this. George awakens from his sedative-induced sleep and causes the plane to crash to the ground. However due to his quick thinking, Davis saves himself, Kate, and Russell from getting killed, and George himself also survives, having sustained a few minor wounds.
Kate informs Davis of an antidote for the pathogen which while it wouldn't revert the animals back to their default sizes, it would neutralize their aggression. As they were trying to find the antidote in Energyne, they are confronted by Claire and her brother, Brett. Claire forces the two to give them the antidote, shooting Davis into submission. However, Kate manages to slip the cure into Claire's handbag, and pushes her towards the direction of George. To her horror, George picks her up and she was eaten whole, before destroying the transmitter. Claire's brother attempts to flee, only to be killed soon after by falling debris.
- Claire was wearing a low-cut, red dress by the time she was eaten by George, which is a nod to the original Rampage video game. In the game, a voluptuous woman in a red dress periodically appeared in a building window, which you could choose to either save (for extra points), or devour. Clearly, George had no intention of getting extra points in the movie.
- In an interview with comicbook.com, when asked how she felt about playing a "transparently bad, evil, woman", Ms. Akerman stated that "we all have a little bad in us", followed by, "it's so much fun; It's so juicy playing the villain".