Plot
After surviving the attack in Lake Placid: The Final Chapter , Jim Bickerman; due to his injuries, is left with an eye patch, hook and wooden leg. Working in Black Lake, Maine, with another mercenary named Beach, they capture a female giant crocodile. They take it back to their truck, where two scientists crossbreed its blood with a female giant anaconda to perfect a Blood Orchid serum. However, the crocodile escapes, killing a scientist, and freeing a female and two male anacondas before causing the truck to explode. The explosion destroys part of the electric fence keeping the crocodiles in Black Lake. Beach, Bickerman, and the one remaining scientist survive. A small group of crocodiles also escape.
The crocodiles search for food and one kills Daphne Mailer and her boyfriend, while another kills the remaining scientist, and multiple baby crocodiles kill a poacher. The crocodiles eventually make their way to nearby Clear Lake, along with the anacondas.
Reba, now the sheriff of Black Lake, calls U.S. Fish and Wildlife Service officer Will "Tully" Tull to help recapture the escaped crocodiles. Meanwhile, a group of college sorority girls from Delta Gamma, led by Tiffani and Amber, and two fraternity boys from Sigma Phi, Brett and Andrew, arrive at Clear Lake to initialize some new members, including Margo and Tully's daughter, Bethany.
The crocodiles feast upon sorority girls along with Amber (whom Tiffani pushes towards the crocodiles), Brett, Andrew, and Heather (the latter three who were wakeboarding). The survivors run into the forest to get to the cars. The girls left the keys on the beach, but the crocodiles attack the students. One of the girls, Cassie, runs out of Jennifer's car, try to escape, but a crocodile eats her. Tiffani's car is crushed by an anaconda with Jennifer still inside. A crocodile kills Tiffani and the others flee.
Deputy Ferguson discovers one of the surviving sorority girls hiding on a boat. The traumatized girl, Melissa, is taken to a hospital, while Tully and Reba continue to search for Bethany. Clear Lake is evacuated by Ferguson.
Sarah Murdoch, the sociopathic daughter of the late Peter "J.D." Murdoch and CEO of Wexel Hall Corporation in New York, leads a team of herself, Beach, Bickerman, and two mercenaries and go to capture the female anaconda before it lays its eggs, hoping to finish her father's work. One of the mercenaries is attacked by a crocodile, and Beach is forced to shoot them both.
Tully and Reba are attacked by a crocodile, which is in turn attacked by an anaconda, which crushes the crocodile until it explodes. The anaconda then escapes. Sarah's group steals a boat, but Bickerman falls off and is dragged underwater by a crocodile. After landing, the other mercenary is killed by an anaconda. Tully and Reba kill the other anaconda and rescue Bethany, Margo, and Jane. They regroup along with Ferguson until Sarah and Beach arrive. They discover two crocodiles eating a male anaconda. The female anaconda appears and kills a crocodile, and a crocodile flings the male anaconda into a helicopter containing Sarah's extraction team, causing it to crash. The female anaconda kills the crocodile and eats Beach alive, who sacrifices his life by detonating a grenade and killing the anaconda that swallowed him, devastating Sarah's chances of completing her father's project. Sarah is arrested and Bickerman, who survived, emerges from the lake, laughing maniacally. One last crocodile appears, but Reba and Tully quickly kill it.
In the nest of eggs laid by the female anaconda, one egg hatches to reveal a baby anaconda with crocodile-like attributes.
