In 2028, Earth is suffering from a global energy crisis. The space agencies of the world prepare to test the Shepard particle accelerator aboard the orbiting Cloverfield Station, which would provide Earth with infinite energy, while conspiracy theorists fear it will create the "Cloverfield Paradox", opening portals to parallel universes allowing their horrors to threaten Earth. Among the crew is Ava Hamilton, a British engineer who frets about leaving her husband Michael potentially for years, as their relationship struggles since the loss of their children to a house fire. The crew is rounded out by American commander Kiel, German physicist Ernst Schmidt, Brazilian medical doctor "Monk" Acosta, Irish engineer Mundy, Russian engineer Volkov, and Chinese engineer Tam.
After about two years of unsuccessful attempts to activate the Shepard, the crew achieves a seemingly stable beam, but it overloads and creates a power surge on the station. After restoring basic power, they find that Earth has vanished from view, and the gyroscope that aids in the station's navigation is missing. As the crew works on repairs, strange events begin to occur, including the discovery (and subsequent rescue) of an unfamiliar woman called Mina Jensen fused with wires inside a wall. Volkov's eyeballs begin moving of their own accord; he begins conversing with his own reflection in a mirror and is compelled to craft a gun using an on-board 3D printer. He uses the gun to threaten the crew, but as he does so he convulses and dies, and the station's worm colony bursts out of him. Jensen tells Hamilton not to trust Schmidt, who Jensen claims to be a spy sent by the German government to keep the Shepard shut down. Mundy's arm gets pulled into a solid wall and is severed clean off, without bleeding or pain. They find the arm roaming of its own volition. When they recognize it is trying to write something, it instructs them to "cut Volkov open". Once they do, they find the missing gyroscope. They finally locate Earth and begin restoring their communications, but transmissions state the station was destroyed and fell to Earth two days prior.
The crew determine the particle beam overload has activated the Cloverfield Paradox, which is the cause of the strange events, and also moved the station to a parallel universe in which Jensen replaced Tam as the station's engineer, Schmidt is a spy, and Hamilton (though still working on the mission) has remained on Earth, where her children are still alive. Believing the Paradox can be reversed and they can return to their own universe if they reactivate the Shepard, the crew starts making repairs. Tam is trapped in a chamber that floods with water, and then explodes, freezing the water and Tam. Meanwhile, Hamilton decides to return to parallel Earth with Jensen in order to prevent the fire that killed her children. As they prepare, Mundy is killed in an explosion caused by a strange magnetic field, destabilizing part of the Shepard and threatening to tear the whole station apart. Kiel sacrifices himself to save the station, leaving Hamilton in charge.
On Earth, Michael has woken up to discover a wave of destruction ravaging the planet, witnessing the silhouette of a giant monster in the distance. On his way to offer assistance at the local hospital, he stops to help a young girl named Molly at a dockyard. After finding the hospital was destroyed, he takes her to the underground shelter of a friend and tends to her wounds.
With the Shepard particle accelerator ready to activate again, Hamilton prepares to leave with Jensen, but Jensen suddenly knocks her out. Jensen kills Monk with Volkov's gun, wounds Schmidt, and insists the station must stay in her universe to keep the Shepard particle accelerator there. Regaining consciousness, Hamilton uses the gun to shoot out a window, ejecting Jensen into space. Hamilton decides to return to their universe with Schmidt and makes a recording she sends to her alternate universe self, with the plans for the Shepard and in which she stresses the importance of her family. Hamilton and Schmidt reverse the universe shift and use Tam's modifications to finally make the Shepard work. After reporting in, the two eject themselves in an evacuation capsule towards Earth.
Michael learns from mission control of the station's reappearance and his wife's return to Earth, but he lambasts them for returning to Earth in light of the ongoing situation. As the capsule re-enters the Earth's atmosphere, a giant monster bursts through the top of a cloud layer, letting out a roar.
