On the Amazon River, a poacher hides from a creature in his boat. He shoots himself rather than have it devour him. Meanwhile, a film crew is shooting a documentary about a long-lost tribe called the Shirishamas. The team is led by director Terri Flores (Jennifer Lopez), cameraman Danny Rich (Ice Cube), production manager Denise Kalberg (Wari Whurer), her boyfriend sound engineer Gary Dixon (Owen Wilson), narrator Warren Westridge (Jonathan Hyde), anthropologist Doctor Steven Cale (Eric Stoltz), and the captain of the boat Mateo (Vincent Castellanos). They run into a stranded Paraguayan snake-hunter named Paul Serone (Jon Voight), who convinces them he can find the Shirishamas tribe for them.

They don’t quite trust him and Doctor Cale argues with him about tribal lore. Eventually, the Doctor is stung by a wasp and is rendered unconscious. Serone performs an emergency operation on him, supposedly saving his life, but soon he takes over the boat and forces the group to do what he really wants, to track down and capture a giant anaconda he has been tracking. Danny, Mateo, and Serone search the poacher’s boat and evidence turns up that he and Mateo and Serone were working together to hunt animals. Mateo is killed by the giant anaconda. Serone promises that he will get them out alive, but Gary is crushed to death despite Terri’s attempt to shoot it.

The crew overpowers Serone and binds him. The next day, the boat is stuck at a waterfall. Terri, Danny, and Westridge enter the water to winch it loose. Denise confronts Serone and tries to avenge Gary’s death, but he strangles her and dumps her in the river. The anaconda returns. Westridge distracts it while Terri and Danny get to the boat. Serone breaks free and attacks Danny. The anaconda climbs a tree and attacks Westridge. The crew ends up in the water. Cale wakes up and Westridge is killed. The snake attacks Danny, but Terri shoots it in the head. Serone attacks her. Cale stabs him with a tranquilizer dart and passes out. Danny knocks Serone into the river.

Serone captures Terri and Danny and uses them as bait to capture a second, larger anaconda. It seizes Terri and Danny and begins to suffocate them. Serone tries to catch it in a net, but it swallows him whole. The anaconda chases Terry, who flees into a nest of baby anacondas. The snake regurgitates a partially digested but still-living Serone and chases Terri up a smokestack. Danny pins it to the ground with a pickaxe and sets it on fire. Finally, Danny kills it with an axe to the head. The survivors are helped to escape the Amazon by the Shirishama tribe.

The film was directed by Luis Lhosa, produced by Verna Harrah, written by Hans Bauer, Jim Cash, and Jack Epps Jr. It received mostly negative reviews but was a box-office success, became a cult classic, and was followed by a series of films, mostly direct-to-video. The Official Razzie Movie Guide placed it on the 100 Most Enjoyably Bad Movies Ever Made list. It was nominated for six Razzies but lost most of them to The Postman. But it made three times its budget in the end. It was in fact pretty damned exciting, and the snake was a star.

The animatronic anaconda shorted out now and then and lost control, but they kept the footage. Many of the cast members were terrified of snakes. The anaconda cost $100,000 a second. Anacondas are cannibalistic, the bigger females often eating the smaller males. In a famous blooper scene, the waterfall goes up. Director Luis Lhosa wanted John Barry to do the score, but he was ill. But Randy Edelman wrote the score in John Barry’s style. Once he had discovered baby anacondas, Serone did not need the adult anymore; they are easier to catch and grow very fast.