A meteor strikes a lighthouse on the coast of Florida, and a glowing field called the Shimmer starts to spread from it. Three years later, biologist and former soldier Lena is questioned by a man in a hazmat suit, Lomax, about what happened inside. The story is told in flashbacks.
Lena's husband Kane, a soldier, disappeared on a secret mission a year ago. One night he walks back into their home, unable to explain where he has been. He suddenly coughs up blood and collapses, and on the way to hospital the ambulance is stopped by government agents. Lena wakes up in Area X, a secret base at the edge of the Shimmer. Psychologist Dr. Ventress explains that every team that went in disappeared, and Kane is the only person ever to come back. Lena joins Ventress's next team: paramedic Anya Thorensen, physicist Josie Radek and geologist Cass Sheppard.
Inside, the women lose days without remembering them, and radios and compasses fail. They find strange, blended plants and animals. A mutated alligator with shark-like teeth attacks them. At an abandoned base, they find a video left by Kane's team, in which Kane cuts open a soldier's belly to show his insides moving like a snake. Lena studies cells under a microscope and finds that the Shimmer is changing their own bodies too. Josie explains that the Shimmer works like a prism, but for DNA: it refracts and mixes everything, including them.
At night, a huge mutated bear drags Cass away and kills her. Anya, now paranoid, discovers that Lena lied about being Kane's wife and that her own fingerprints seem to be moving. She ties up the others. The bear returns, screaming with Cass's dying voice, and kills Anya before Josie shoots it dead. Josie, who has self-harm scars and has long felt numb to life, walks into the garden and turns into a plant-like person. Ventress, who has terminal cancer, goes ahead alone to the lighthouse.
Lena reaches the lighthouse and finds Kane's burned remains and a camera. The video shows Kane killing himself with a phosphorus grenade, after which a perfect copy of him appears. Underground, Ventress tells Lena the Shimmer is not destroying things but making something new, then dissolves into a ball of light. A drop of Lena's blood creates a faceless, shiny humanoid that copies every move she makes and slowly takes her shape. Lena tricks it into holding a phosphorus grenade and escapes as it burns and the lighthouse catches fire. The whole Shimmer collapses.
Back in the present, Lomax asks what the Shimmer wanted, and Lena says she does not know. She visits the recovered Kane. He admits he does not think he is Kane, and asks if she is Lena. She does not answer, and they embrace as both their eyes shimmer.