Plot
On the Amazon River, a poacher hides from an unknown creature in his boat. When it breaks through the boat and attempts to trap the poacher, he commits suicide by shooting himself to prevent it from killing him.
Meanwhile, a film crew is shooting a documentary about the Shirishamas, a long-lost indigenous Amazonian tribe; the ensemble consists of director Terri Flores, cameraman and childhood friend Danny Rich, production manager Denise Kalberg, Denise's boyfriend and sound engineer Gary Dixon, narrator Warren Westridge, anthropologist Professor Steven Cale, and boat skipper Mateo. The group encounters stranded Paraguayan snake hunter Paul Serone, who convinces them he can help them find the Shirishamas. Most of the crew are uncomfortable around Serone, and Cale clashes with him several times about Shirishama lore. Eventually, Cale is stung by a wasp, and an allergic reaction swells up his throat and leaves him unconscious. Serone performs an emergency cricothyrotomy, seemingly saving Cale's life, but soon after takes over the boat, forcing the group to help him achieve his true goal: hunting down a giant record-breaking green anaconda he had been tracking, which he believes that he can capture alive.
Danny, Mateo and Serone search the wreckage of the poacher's boat. A photograph in an old newspaper reveals that Mateo, Serone, and the poacher were working together to hunt animals, including snakes. Leaving the poacher's ship, Mateo falls into the water, where the giant male warrior anaconda, measuring 25 ft (7.6 m), ambushes and kills him, while the other two return to their boat, unaware of Mateo's fate. Serone manipulates Gary into helping him ensnare the creature which might get him one million dollar in price. That night, he uses a dead monkey as bait to catch the creature, which proceeds to emerge and attack the crew. He attempts to capture the snake, but it coils around Gary, crushing him. Serone thwarts Terri's attempt to shoot the anaconda to rescue Gary, whom it devours, devastating Denise. The crew overpowers Serone and ties him up as punishment.
The next day, the boat becomes jammed near a waterfall, and Terri, Danny, and Westridge enter the water to winch it loose. Denise confronts Serone and attempts to kill him to avenge Gary's death, but he ambushes and strangles her with his legs before dumping her corpse into the river. When the creature returns, Westridge distracts it long enough for Terri and Danny to retreat while he ascends the waterfall. Serone breaks free during the attack and assaults Danny. The snake mounts a tree branch and attacks Westridge, unintentionally uprooting the tree, and he perishes in the subsequent fall. The tree falls onto the boat, subsequently awakening Cale, and Serone, Danny, and Terri escape by jumping into the river. The snake resurfaces and attacks Danny, but Terri, having reboarded the boat, rescues him by shooting one of its eyes out. Serone, still believing he can capture it alive, reboards the boat and pulverizes her. Cale rescues her by stabbing Serone with a tranquilizer dart before losing consciousness again himself, and Danny pummels Serone into the river.
Serone eventually catches up to the group and captures Terri and Danny, drenching them with animal blood to bait a second, much larger female Queen anaconda, measuring 40 ft (12 m); it attacks the pair, slowly suffocating them. He tries to catch it in a net, but it breaks free and attacks him, eventually swallowing him whole, which the pair observe while escaping their respective bonds. It chases Terri into a building, where she encounters a nest full of newborn anacondas, then regurgitates the still-alive, but partially digested Serone, who winks at Terri, and chases her up a smokestack. Danny pins its tail to the ground with a pickaxe and ignites a fire below the smokestack, setting the snake ablaze; the resulting explosion sends the burning anaconda flying out of the building and into the water. As Terri and Danny recuperate on a nearby dock, the creature resurfaces, but he slaughters it with an axe to the head.
Afterward, the pair reunites with Cale, who begins recuperating on the boat. While floating downriver, the trio locates the Shirishama tribe they were originally seeking and, realizing Serone was right, begins filming their documentary.
