Kepler 822, a research and drilling facility operated by Tian Industries at the bottom of the Mariana Trench, is struck by a strong earthquake. As part of the facility is destroyed by the quake, mechanical engineer Norah Price and her colleagues, Rodrigo and Paul, make their way to the escape pod bay. However, the three discover that all of the escape pods have already been deployed, with Captain Lucien being the only person in the area when the three arrive. Together they reach a control base and find biologist Emily Haversham and engineer Liam Smith, who are unsuccessful in their attempts to make contact with the surface. Lucien suggests using pressurized suits to walk one mile across the ocean floor to Roebuck 641 in the hope of resurfacing from there. As they descend in a freight elevator, Rodrigo’s defective helmet implodes under the water pressure. The surviving crew see a distress beacon from one of the escape pods below, and Smith and Paul go to investigate. As they arrive at the location, they find a body in the rubble. A creature emerges from the corpse’s back and attacks. Smith kills the creature and takes it inside. Haversham examines the creature and realizes that it belongs to a previously undiscovered species.
The five make their way to the sea floor, but as they are walking, Kepler explodes above and nearly buries them in debris. Smith is hit, but Price and Lucien save him. They manage to get through an access tunnel to an intermediate station, where they can charge and clean their suits. However, they find that Smith’s oxygen scrubber is badly damaged from the debris. On their way through the access tunnel, Paul is attacked by an unknown creature, dragged underwater and killed. Before the team leaves the access tunnel, they find that Smith’s damaged oxygen pod will cause him to suffocate from the explosion’s toxic fumes. Unwilling to leave another crew member behind, Price, Lucien and Haversham agree to help Smith walk. The four set off across the ocean floor, but a humanoid creature appears and drags Smith into a cave. Lucien manages to get Smith out, but is himself pulled from the other three. Price is dragged along with Lucien, but Lucien sacrifices himself to spare Price from the increasing pressure differential.
Price ends up at the abandoned Shepard station alone, where she rummages through Lucien’s locker to find a pentagram drawn on an old blueprint of the initial drilling site. Price is able to change her damaged diving suit before continuing toward Roebuck. Walking along the ocean floor, she reunites with Haversham and Smith, and proceeds to help drag Smith. As they enter Roebuck, they encounter a nest of the humanoid creatures hanging from the ceiling and try to sneak by, but the sound of Haversham’s oxygen alarm wakes the creatures. Price is partially swallowed by one of the creatures, but is able to kill it and free herself by firing her flare gun while inside of its body. She then fires a second flare into the distance and sees the creatures are spawn to an ancient titanic creature, Cthulhu. The three manage to reach the escape pod bay, but Price discovers that only two of the pods are functional. Price and Haversham manage to get the ailing Smith into a pod, and Price persuades Haversham to take the last one. As this happens, Cthulhu emerges and attacks the Roebuck while the smaller creatures follow the two escape pods. Price, accepting her impending death, initiates an overload of the Roebuck’s nuclear core, resulting in a massive explosion that engulfs her, Cthulhu, and the creatures and allows the escape pods to reach the surface. Tian Industries refuses involvement with investigations into the events and prepares to expand its drilling efforts.