Near the Great Pacific garbage patch, marine researcher Sophia Assalas and her team search for Lilith, a tagged shortfin mako shark. Her husband Chris leads a dive team of Sam, Juan and Tom, leaving Sophia and Jade onboard. The team first observe an unusual sight of makos hunting in a pack, before they locate Lilith, who has grown much larger since she was last sighted. With the shark appearing non-aggressive, Chris attempts to take a blood sample from Lilith, but the shark suddenly snaps and kills him, Sam, Juan and Tom. Leaving the safety of the boat, Sophia goes after Lilith, but becomes entangled in a net and dragged far beneath the surface as the shark escapes into the depths. She manages to free herself, but not before suffering injuries due to the severe change in pressure.
Three years later, Sophia works at an aquarium in Paris. Mika, an environmentalist, informs Sophia that Lilith’s tracking beacon is still active and that she has travelled from the Pacific and up the River Seine and is seemingly trapped in the city. After a man is found dead with wounds from shark bites, police diver Adil recruits Sophia to help find and kill the shark, but Mika and her girlfriend Ben turn off the beacon before they can do so in the hope that they can rescue her later. Sophia and Adil petition the Mayor of Paris to postpone the upcoming triathlon. The mayor refuses, emphasizing the event’s importance for focusing global attention on Paris during the run-up to the Olympic Games which billions of euros have already been spent on. Mika reveals Lilith’s existence to the public, and leads a group of supporters into the city’s catacombs, where the city’s wastewater reservoirs are, to find her. Ben tells Sophia of Mika’s plan, and she and Adil’s team head down into the catacombs to find them after reactivating Lilith’s beacon.
Mika activates a pulse to lure Lilith to where her group have convened, and swims out to the middle of the reservoir. Adil’s team arrives just as Lilith appears with a juvenile shark, Lilith’s offspring. Mika refuses to hear warnings to get out of the water, and after she pets the juvenile shark, Lilith attacks and kills her, causing a mass panic that leads to many injuries and twelve deaths, including that of Ben and of Leopold, a police officer on Adil’s team. In the aftermath Sophia and Adil find the juvenile shark dead, and after examining it they discover that it has mutated to adapt to fresh water and that it is pregnant through parthenogenesis, and that if not caught Lilith may give birth to more mutated offspring. The Mayor, deflecting blame from herself, orders them to kill the shark, and still refuses to cancel the triathlon to be held in the river the following day. She takes part in a TV interview downplaying the danger the sharks present.
Sophia and Adil devise a plan to lure Lilith out of the catacombs and blow her up with the help of explosives experts Poiccard and Berruti. As the mayor declares the triathalon open, and swimmers take to the water, Adil’s team Caro, Adama, Angèle and Markus begin to execute the plan. Underwater, Sophia and Adil encounter a large school of juvenile sharks as they set up their trap. The sharks kill Poiccard, Berruti and Adama before Adil sets the explosives off, seemingly destroying the school of young sharks and leaving the gigantic Lilith as the only survivor. She capsizes the police boat, killing Caro and Markus, and she heads towards the triathlon. The mayor and the spectators look on in horror as several swimmers are attacked and killed. The military open fire on Lilith, despite warnings from Adil that there are live shells on the riverbed. The disturbance in the water from their gunfire and Lilith’s movements causes unexploded ordnance at the bottom of the river to shift and detonate, throwing the Mayor, Angèle, and many spectators into the water. The resulting chain reaction of explosions destroys several bridges and creates a tsunami that entirely floods the center of Paris. Sophia and Adil are left stranded on the roof of a building in the middle of the flood, surrounded by Lilith and the juvenile sharks that have survived the explosions.
As the end credits suggest, Lilith and her offspring have proliferated in the major river cities of the world (Paris, London, New York, Bangkok, Venice and Tokyo), and seem to have, as Sophia feared, colonized the entire world.