Jackson Oz is asleep at a safari camp in Botswana, as Daniel, a teenage boy watches videos of Robert Oz, Jackson's father, on a laptop beside him. Daniel's father, Abraham, enters the tent to wake Jackson, and remind him of the tour group he is taking out to see rhinos shortly. Daniel asks Jackson what Robert means in his videos when he talks about "the defiant pupil" but Jackson quickly dismisses his question, saying that everything his father says in those videos is gibberish.
While Jackson and Abraham are out on the rhino tour, they see a hunter ahead pulling a gun out, ready to shoot a rhino. Abraham hands Jackson an old-school boom box, and he holds it up over his head blasting James Brown's, "Get On Up." The rhino is alerted, and runs away, and the hunter is not very happy with Jackson. He argues to Jackson that he has a valid hunting license, and the verbal confrontation becomes very tense. The tension is only broken when Abraham appears at Jackson's side, and the hunter backs down.
In Los Angeles, Jamie Campbell, a newspaper reporter, is on the phone trying to gather information about a recent zoo attack. Two lions broke out of their habitat, and went of a rampage killing their trainer, and several citizens, before they were shot and killed. Jamie is convinced that this must be due to a food change, the food now being supplied by a global biotech company that Jamie has a hatred for. While on the phone, Jamie's boss pulls her into the editor's office. It seems that Jamie has been running a blog that has some people very angry, namely the global biotech company that she has been disparaging, that also happens to own the newspaper she works for. Jamie is let go, but refuses to stop investigating the lion attack story.
Jamie heads to a birthday party in the backyard of a Los Angeles parks and recreation employee who has been the face of the news reports regarding the lion attacks. While questioning him about the food change, he asks her to leave him alone, and tells her that if she really wants to chase a story, she should be looking for the missing cats. Dozens of cats have been abducted recently, including his own. Jamie leaves the party, confused as to why so many cats are suddenly disappearing.
Jackson and Abraham are headed to another safari camp, this one belonging to Abraham's cousin, Simon. While on the journey, Abraham decides that he will mention Daniel's growing interests in the animals to Simon. Jackson says that if Daniel really wants to be a scientist like Robert Oz, then he will stop watching his tapes. According to Jackson, his father's tapes are nothing but videos of "a brilliant man coming unhinged."
When Jackson and Abraham arrive at Simon's camp, they find it has been abruptly deserted. Food still sits on plates, iced tea still in glasses, but tables and chairs have been knocked over, and all of the vehicles are missing. They begin to investigate to find out what would cause the entire camp to suddenly evacuate. Jackson finds a clue in a video camera that has been left behind. On the video, a man is enjoying his lunch, chatting with his friend about a French woman, when suddenly the camera begins to shake and we hear animal snarls and roaring. The camera goes blank.
Jackson and Abraham decide to go out to looking for anyone left behind, or to find any other clues as to what happened. They come across Simon's truck, and Abraham hears moaning inside, and enters the truck to help whoever is inside. Jackson stays outside, keeping watch for anything unusual, when he hears a rustling in the grass, he quickly scans for an animal, but is knocked down by a woman, who is frantic and screaming. Jackson turns to find there is a lion headed for the truck. Jackson shoots at the lion, but he is too late, and he realizes there is a pack of lions headed for them. They find shelter in a truck, and narrowly escape the lions.
Once Jackson and the woman, Chloe, are a safe distance from harm, she begins to tell him what happened at the camp. They were on a gazelle safari when a pack of lions suddenly came after them. The lions killed Simon, and came after the others next. Chloe wanted to stay and help others, but she knew that if she did, she would also be killed. So she ran. The car breaks down, and the pair have until the sun goes down to reluctantly walk to a safe shelter.
The lion pack finds them again, this time backing them to the edge of a cliff. Just as they are about to fall over the edge, one of the lions looks into Jackson's eyes and roars. Jackson's eyes widen as he sees it: the defiant pupil. They go over the edge.
Back in Los Angeles, Jamie meets up with Mitch Morgan, an animal pathologist who is also investigating the lion attacks. He takes Jamie to the animal morgue and shows her the lion bodies. Jamie shares her food theory with Mitch, and he immediately shoots it down, telling her that food would not have caused such an abrupt change in the lion's behavior. Mitch declares that sometimes a mystery is just a mystery, and Jamie mentions the missing cat mystery. He apologizes that he can't be more help. She gives him her phone number in case he thinks of anything, and they part ways.
Later that evening, Jamie gets a call from Mitch. She meets him at an elementary school, where he explains that he couldn't stop thinking about the missing cats. He decided to take a look around town, and on his search, he found the cats. He points his flashlight up to a tree, where dozens of cats are perched on the branches.
Jackson and Chloe, safe from their slide down the cliff, arrive at a camp. Jackson begins to explain his father's work to Chloe, the work that ultimately drove him insane. In his manifesto tapes, Robert talked about a defiant pupil in animals. Jackson always assumed that Robert was speaking about one of his students, but earlier, he saw the defiant pupil in the lion's left eye just before they fell. Now, Jackson is beginning to wonder if his father wasn't as crazy as he once believed.
Chloe and Jackson have radioed for help, and are enjoying coffee when trucks pull up. The police have arrived, not to help them, but to arrest Jackson. It seems the hunter from earlier feels that by interrupting his hunt, he was committing a crime. Jackson tries to explain to the police that there is something wrong with the animals, but they don't want to hear it. They drive off, Jackson handcuffed in the back of the car.
Daniel is again watching Robert's videos in his tent. Over his shoulder, several pairs of eyes are shining in the darkness.
A lion is dragging a body up a tree. The lion saunters away, and in the tree is Abraham, still alive.