While carrying out his research as a travel journalist, cynical American Pete McKell joins a group of tourists on a crocodile watching river cruise in Kakadu National Park of Australia's Northern Territory, led by wildlife researcher Kate Ryan. After a run-in with two locals, Neil and Collin, the cruise winds to a close and Kate prepares to return the group to base.
Everett spots a flare in the distance, and Kate tells the group that they must investigate to determine whether someone needs rescuing. A few miles up river, they come across a half-sunken wreck when suddenly, something crashes into the tourists' boat, creating a crack in the side. Kate's only choice is to run it ashore on a small island in the middle of the river. The group disembarks and begins discussion of what to do when Everett is suddenly pulled into the water by an unseen predator and killed. Kate comes to the conclusion that they are in the heart of a large crocodile's territory and that it will be more aggressive than usual. The tourists realize that by nightfall, the tide will start to rise and in a matter of hours, their small island will be submerged.
Neil and Collin arrive soon after, and as they near the island, an unseen force, smashes their boat and sinks it. Neil manages to swim to the island safely, but Collin disappears.
As night falls, Neil suggests that he swims to the riverbank in order to string a rope between two trees, creating a zip-line that will allow the group to cross the river. Neil succeeds in setting up the rope and Mary Ellen crosses first, only to freeze in fear halfway across. Allen becomes impatient and aggressive and attempts to get himself and his daughter Sherry across with Mary Ellen still on the line. While trying to secure the rope, Neil is attacked by a crocodile and killed. The tree holding the rope breaks and the three on the line fall into the water. They manage to swim back to the island, but as Allen crawls up the beach, the gigantic 25-foot crocodile suddenly lunges out of the water, rips off his right arm, and throws him into the middle of the river, where he is dragged under and killed.
Later that night, Pete suggests they can delay the crocodile with a hook and bait on one side of the island while everyone escapes off the other side. Simon is skeptical of the idea, but Russell agrees to try. Lacking bait, everyone suggests using Kate's dog Kevin, but they decide to use two dead birds that Neil and Collin had shown them earlier. Kate hooks the birds onto the boat's anchor while Pete secures the other end of the rope to a boulder and throws the bait out into the river. After a long wait, the anchor is suddenly grabbed and pulled and the group makes a break for the far shore. Russell assists Sherry's mother, Elizabeth, due to her inability to swim. Pete tries to stop the boulder from being pulled over as Kate swims across behind the group. The crocodile suddenly lets go of the hook and bait, seizes Kate, and drags her underwater. Pete hurriedly makes the swim across the river with Kevin in tow, and heads off into the bush to meet up with the others.
As day breaks, Pete is crossing a stream when Kevin runs away. Pete chases the dog into a cave and falls down a narrow chute into a larger cave, where he sees Neil's corpse. He realizes that the cave is the crocodile's lair, and to his surprise, he finds Kate alive, but badly injured and unconscious. He attempts to carry her out but has to hide when he hears the crocodile returning and Kevin is devoured. Finishing its meal of Kevin, the crocodile enters the cave and falls asleep. Trying to reach the entrance carrying Kate, Pete awakens the crocodile, and it makes several attempts to kill both him and Kate as he retreats into the narrow confines of the cave. Finally, after a fight in which he gets tossed around and is severely bitten on the hand, Pete makes one desperate last stand. He braces a broken log against a large boulder with the sharp end pointing out towards the crocodile. The crocodile lunges at him, and Pete successfully impales it through the head, killing it. He escapes from the cave with Kate to join the surviving tourists and waiting paramedics.
As the credits roll, the camera zooms in on a newspaper article detailing Pete's heroic battle with the crocodile and rescue of Kate.
- Michael Vartan as Pete McKell
- Radha Mitchell as Kate Ryan
- Sam Worthington as Neil
- Stephen Curry as Simon
- Celia Ireland as Gwen
- John Jarratt as Russell
- Heather Mitchell as Elizabeth
- Geoff Morrell as Allen
- Mia Wasikowska as Sherry
- Caroline Brazier as Mary Ellen
- Robert Taylor as Everett Kennedy
- Barry Otto as Merv
- Damien Richardson as Collin