The movie happens in flashback as Lena is interrogated by Lomax and a group of people in hazmat suits.

Three years ago, something crashes into a lighthouse in a column of rainbow smoke.

Kane, Lena's husband, arrives out of the blue while she's painting the bedroom. They have a short conversation before Kane spits out blood into the cup of water he's drinking. By the time an ambulance arrives, he's seizing. While the ambulance is taking Kane to the hospital, they're suddenly run off the road by the police and military, who take Kane and Lena.

Lena wakes up in a cell in the Southern Reach facility and has a conversation with a psychologist, Dr. Ventress, who tells her that Kane is dying of multiple organ failure.

Ventress shows Lena the Shimmer, the border between their world and Area X. The Shimmer looks like an oil slick floating in the air, refracting light into rainbow patterns. People go in and never come out in the effort to identify the Shimmer's source and prevent it from continuing to destroy the world. And it's advancing.

That night, Lena meets some Southern Reach employees: Anya, a bisexual paramedic; Cassie, a geomorphologist who studies magnetic fields around the earth; and Josie, an astrophysicist who studies the lifecycle of stars. Despite the failure rate of expeditions into Area X, all three of them, along with Ventress, will be embarking on an expedition in a few days.

Lena asks to join them.

They go inside the Shimmer. They encounter a mass of mutated flowers. A large albino crocodile attacks Josie and then approaches all four of them. Lena shoots it down and it's also fucked up and mutated with many concentric rings of teeth.

They find an abandoned military fort with bad vibes. There's a memory card left in a ziploc bag labeled "for those that follow". In the video, a man is tied to a chair. Kane cuts a large window of flesh in the man's abdomen, reveal rolling snakes inside him, like his intestines were replaced with large worms. Ventress leads them to where in the fort the incident occurred, where instead of a body has been mutated lichen and spores on the wall. Split in half, skull wrenched open.

That night, Lena wakes up from a nightmare and joins Ventress on her guard shift. They hear something, prompting Cassie, then Anya and Josie, to run down and join them. Lena notices a large hole in the fence and Cassie is dragged away by a large carnivorous creature. She screams for help until she stops.

The next morning, Anya and Josie want to leave. Ventress blows them off and leaves without them, determined to get to the lighthouse. After the disagreement, Anya confronts Lena, forces her to "pick a side" between going back with them or looking for the lighthouse with Ventress. Lena says she agrees with them, but she lies and tells them that going toward the lighthouse/coast is the better way to do it. They follow, Anya increasingly suspicious. She's extra slighted later when, after discovering Cassie's shoe, Lena sets out alone to determine if Cassie is alive—and she is not.

That night, Anya knocks Lena out and when she wakes up she's gagged and tied to a chair. Anya confronts her with the locket with Kane's picture in it, worrying that Lena actually killed Cassie. She says that she didn't see a bear, so she has to trust Lena about the whole thing, but now she thinks Lena is a liar for not revealing about her relationship to Kane. Before Anya can do anything violent, they hear Cassie's voice screaming out for help, and Anya runs out after her.

A horrifying creature like a bear with an elongated skeletal face enters the house where Ventress, Josie, and Lena are tied up. When it roars, it sounds like Cassie screaming for help. Anya comes back to shoot the bear, but it retaliates and rips Anya's throat open and tears off her lower jaw. It goes for Lena but Josie shoots the creature in the head with a machine gun until it dies.

Ventress leaves in the night, leaving Lena and Josie behind. The next morning, Josie shows Lena that plants are growing out of her scars. She gives into the mutations, leaving Lena alone.

Lena finds the coast and then the lighthouse. As she gets closer, glass crystal trees litter the beach, and there are human skeletons arranged rituallistically at the base.

Inside is a hole surrounded by concrete lichen. Next to it is a charred skeleton sitting on the ground. Across is a video camera. When Lena plays the video, she sees Kane address the cameraman before killing himself with a phosphorous grenade. After the grenade goes off, the camerman is revealed to be Kane. Or, Kane, too.

Down below the hole, something can be heard. Lena enters the entry wound that looks like rippled and refracted stone and earth, turned obsidian with heat. In a center chamber is Ventress, her skin soft and green, skin covering her eyes. When Lena approaches her, she returns to normal.

Ventress erupts with a golden fractal, waves of shimmering brilliance, erupts from her mouth and fills the room, leaving her body behind to turn into nothing but refracted light and something alien and bright that looks out at Lena.

The fractal manifests with a human-like body, green soft and green with oil slicking rainbow. Lena and the form fight, the form copying and mirroring Lena. Using one of the phosphorous grenades, Lena pulls the pin and runs, leaving the body to absorb the explosion. The body begins to disintegrate, burning with white flames that take over the lichen on the lighthouse wall and then the lighthouse wall itself. Still aflame, the body crawls back down into the hole and into the central chamber. The fire refracts, setting the glass trees on the beach on fire.

The Shimmer fades. Everywhere.

Kane is healed and Lena inexplicably returns intact. Lena and Kane reunite, eyes shimmering.