In 1979, an American film crew disappears, in an area of the Amazon rainforest known as the “Green Inferno”, while filming a documentary about indigenous cannibal tribes. The team consists of Alan Yates, the director; Faye Daniels, his girlfriend and script girl; and two cameramen, Jack Anders and Mark Tomaso. Harold Monroe, an anthropologist at New York University, agrees to lead a rescue team in hopes of finding the missing filmmakers. In anticipation of his arrival, the military conducts a raid on the local Yacumo tribe and takes a young male hostage to negotiate with the natives. Upon arrival, Monroe is introduced to his guides, Chaco and his assistant, Miguel.
After several days of trekking through the jungle, the group encounters the Yacumo tribe. They arrange the release of their hostage in exchange for being taken to the Yacumo village. Once there, the group is initially greeted with hostility and learns that the filmmakers caused great unrest among the people. The next day, Monroe and his guides head deeper into the rainforest to locate two warring cannibal tribes, the Ya̧nomamö and the Shamatari. They encounter a group of Shamatari warriors and follow them to a riverbank, where they save a smaller group of Ya̧nomamö from death. The Ya̧nomamö invite Monroe and his team back to their village in gratitude, but they are still suspicious of the foreigners. To gain their trust, Monroe agrees to bathe naked in a river, where he is joined by a group of Ya̧nomamö women. Afterwards, the group emerges from the riverbank to take Monroe to a shrine, where he discovers the skeletal remains of the filmmakers. Angered, he confronts the Ya̧nomamö in the village, during which time he plays a tape recorder. The intrigued natives agree to trade it for the filmmakers’ surviving reels of film.
Back in New York, executives of the Pan American Broadcasting System invite Monroe to host a broadcast of the documentary to be made from the recovered film, but Monroe insists on viewing the raw footage before making a decision. The executives first introduce him to Alan’s work by showing an excerpt from his previous documentary, The Last Road to Hell, which depicts executions in Idi Amin’s Uganda and from the Vietnam War. One of the executives tells Monroe that Alan staged such dramatic scenes to get more exciting footage. Monroe then begins to view the recovered footage, which first follows the group’s trek through the jungle. After walking for days, their guide, Felipe, is bitten by a venomous snake. The group amputates Felipe’s leg with a machete to save his life, but he later dies and is abandoned. The group locate the Yacumo in a clearing, where Jack shoots one in the leg so they can easily follow him to the village. Once they arrive, the crew proceeds to intimidate the Yacumo, abusing and shooting a villager’s pig next to a child, then firing wildly and herding the rest of the tribe into a hut, burning it down in order to stage a massacre for their film.
Monroe finishes viewing the footage alone and expresses his disgust to the station executives regarding their decision to air the documentary. He criticizes the staged scenes and poor treatment of the natives, but his concerns are ignored. To convince them not to show the film, he shows them the remaining, unedited footage that only he has seen. The final two reels begin with the film crew locating and capturing a Ya̧nomamö girl, whom the men take turns raping and filming, against Faye’s protests. They later encounter the same girl impaled on a wooden pole by a riverbank, where they claim that the natives killed her for loss of virginity (although it is heavily implied that they staged the attack to make it look like the villagers did it). Shortly afterwards, they are attacked by the Ya̧nomamö as revenge for the girl’s rape and death. Jack is hit by a spear; Alan shoots Jack, to prevent his escape, so that the team can film how the natives mutilate his corpse. As the three surviving team members try to escape, Faye is captured, and Alan insists that they attempt to rescue her. Mark continues to film as she is stripped naked, gang-raped, beaten, and beheaded. The Ya̧nomamö then pursue and kill the last two team members as the camera drops to the ground in front of Alan’s bloody face. Disturbed by what they have seen, the executives decide to destroy the footage. As Monroe leaves the station, he ponders to himself who the “real cannibals” are.