Four Atlanta businessmen—Lewis Medlock, Ed Gentry, Bobby Trippe and Drew Ballinger—decide to canoe down a river in the remote northern Georgia wilderness before it is dammed. Lewis, an experienced outdoorsman, is the leader; his close friend Ed has been on several trips but lacks Lewis's machismo, while Bobby and Drew are novices. En route to their launch site, the men (Bobby in particular) are condescending towards the locals, who are unimpressed by the "city boys". At a local gas station, Drew, with his guitar, engages a young banjo-playing boy in a musical duel ("Dueling Banjos"). The duel is mutually enjoyable, and some of the locals break into dance at the sound of it. However, the boy does not acknowledge Drew when prompted for a congratulatory handshake.
The foursome travels in pairs and their two canoes become separated. Ed and Bobby land and encounter a pair of mountain men emerging from the woods, one carrying a shotgun and missing two front teeth. Following a verbal altercation, Bobby is forced by the men to undress. The unarmed man rapes him, demanding he "squeal like a pig", while Ed is bound to a tree and held at gunpoint. Just as Ed himself is about to be raped, Lewis sneaks up and kills the rapist using his bow and arrow; Ed retrieves the gun and the remaining mountain man flees into the woods. After a brief but hotheaded debate between Lewis and Drew, Ed and Bobby vote to side with Lewis's plan to bury the body and continue on as if nothing had happened. The four continue downriver but the canoes reach a dangerous stretch of rapids. As Drew and Ed reach the rapids in the lead canoe, Drew shakes his head and falls headlong into the water—it is unclear why.
The canoes collide on the rocks, spilling the three men into the river. One of the canoes is smashed. Lewis breaks his femur and the others are washed ashore alongside him in a gorge. Lewis, who believes Drew has been shot, encourages Ed to climb to the top of the gorge and dispatch the other mountain man, who they believe is stalking them from above. Ed reaches an overlook and hides out until morning, when a man appears above him with a rifle; Ed clumsily shoots and manages to kill him, but falls backwards, stabbing himself with one of his own arrows in the process. The dead man seemingly has all his teeth, but on closer inspection, is revealed to be wearing dentures. Ed and Bobby weigh down the body in the river to ensure it will never be found, and when they encounter Drew's body downriver, they do the same.
Upon finally reaching the small town of Aintry, they take Lewis to the hospital. The men carefully concoct a cover story for the authorities about Drew's death, lying about their ordeal to Sheriff Bullard in order to escape a possible double murder charge. The sheriff does not believe them, but has no evidence to arrest them and tells the men never to come back. The trio vow to keep their story of death and survival a secret for the rest of their lives. In the final scene, Ed awakens, startled by a nightmare in which a bloated hand rises from the lake.
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