Two days after the events of the first film, a traumatized and blood-covered Sarah Carter escapes the cave system with amnesia. She is taken to a hospital, where the doctor notes that some of the blood on her matches the blood type of Juno Kaplan, one of her missing friends. Sheriff Vaines and his deputy Ellen Rios bring along three pothole cave specialists — Dan, Greg, and Cath — to search for the missing women. They are sent to the cave via an old mine shaft operated by an old man, Ed Ed Oswald.
The group discovers Rebecca Vernet's corpse near the entrance, triggering Sarah's memories of the events before her escape. Sheriff Vaines believes she was involved in the disappearances. While crawling through a tunnel, Sarah suddenly attacks Vaines and Greg before fleeing.
When the team splits up in search of her, Vaines accidentally discharges his pistol after a crawler scares him. A portion of the cavern collapses, trapping Cath under a pile of rocks. They seek an alternate route to reach Cath and enter a bone-filled chamber where they find Holly's damaged video camera among the debris. They watch the footage and realize the missing women were attacked by the crawlers. Sarah, hiding nearby, overhears the recording and regains her memories. A panicked Rios begins shouting for help, drawing the crawlers toward her position. Sarah saves her by muffling her mouth, as the crawlers are blind and hunt by sound. The two watch in silence as a crawler kills Dan and drags his body away.
Cath squeezes free, crushes a crawler under the rocks, and encounters Greg again; they escape another crawler and find Sam Vernet's body hanging from the ceiling across a chasm. They consider using her body to swing across but are attacked again. Greg sacrifices himself to buy Cath time. Although Cath reaches the other side, a crawler kills her when she screams Greg's name.
Elsewhere, Vaines is attacked by a crawler but is saved by Juno Kaplan, who is still alive. Sarah and Rios kill a crawler in a pool and soon meet Vaines and Juno, shocked to see Juno alive. Juno is furious that Sarah left her to die after she stabbed her leg with a pickaxe. Juno nearly kills her before Rios lies that Sarah brought them to find her voluntarily. Juno then leads them to a feeding pit, which she claims has a passage to the surface that the crawlers use to gather food from above ground. Vaines handcuffs Sarah to himself so that she will not abandon them as she did to Juno. When he falls over a ledge, he almost drags Sarah down with him. As crawlers close in, Juno orders Rios to cut off Vaines's hand to save Sarah. Despite his protests, she does so, causing Vaines and the crawlers latched onto him to fall to their deaths.
Sarah, Juno, and Rios reach the exit, where they are blocked by a group of crawlers led by their large leader. They try to sneak past but Greg, who is dying from his injuries, appears and grabs Juno's leg in a last effort to save himself. She screams and attracts the crawlers. Greg dies and the women are left to fight once again. After all of the crawlers are killed, Sarah tries to rescue Juno from the leader, but it slashes Juno's stomach, mortally wounding her. Sarah then kills it before Juno dies in her arms. When more crawlers arrive, Sarah draws their attention to herself by screaming, giving Rios a chance to escape.
Rios escapes from the cave and tries to call for help. However, she is knocked unconscious with a shovel by Ed, who drags her back to the cave entrance and leaves her there. As Rios slowly regains consciousness, a blood-covered crawler emerges from the cave with its arms outstretched.
