In the summer of 1979, Joe Lamb (Joel Courtney), a 14-year-old boy living in the fictional town of Lillian, Ohio, has lost his mother in a factory accident. Louis Dainard (Ron Eldard) comes to the wake, but Joe's father, Deputy Jackson Lamb (Kyle Chandler), takes Dainard away in handcuffs. It is later revealed that Jackson blames Louis for his wife's death because he was absent during his shift and she had to fill in for him.
Four months later, Joe's friend Charles Kaznyk (Riley Griffiths) convinces Dainard's daughter Alice (Elle Fanning), who both he and Joe secretly have crushes on, to be the protagonist's wife in his low budget zombie movie on Super 8 film. Alice steals her father's car and takes Joe, Charles, Preston (Zach Mills), Martin (Gabriel Basso), and Cary (Ryan Lee) to an old train depot where the group plans to film a scene. During the shoot, Joe watches a pick-up truck drive onto the tracks and place itself in the path of an oncoming train, causing a massive derailment.
In the aftermath of the accident, the kids find the wreck littered with strange white cubes. They approach the truck and discover Dr. Woodward (Glynn Turman), their biology teacher, behind the wheel of the truck. He instructs them to never talk about what they saw; otherwise, they and their parents will be killed. Moments afterwards, the U.S. Air Force, led by Colonel Nelec (Noah Emmerich), arrives to secure the crash site while the kids flee the scene.
Over the next couple of days, strange phenomena occur: numerous town dogs run away; kitchen appliances, car engines, and power lines vanish, and people begin to disappear. The Air Force deliberately starts a wildfire (Operation Walking Distance) outside of town, giving them a pretext to evacuate the entire town to a nearby base. Upon arriving at the base, Joe finds Louis Dainard, who tells him that a creature abducted Alice. Joe, Charles, Cary, and Martin sneak back into town and head to their school, where they break into Woodward's stash of confiscated items, thinking he may have hidden documentation about the creature that might help them save Alice. In the papers, film, and audio recordings, they discover that the government imprisoned an extraterrestrial (played by Bruce Greenwood in motion capture sequences) who crashed on Earth in 1958. The alien only wished to rebuild its ship, using the shapeshifting white cubes and return home, but it was instead imprisoned and tortured by the Air Force, who sought to seize its technology. One film shows Woodward, a researcher at the time, being attacked by the alien. This physical contact caused him to form a telepathic bond with the alien, through which he learned that it only wanted to go home. Woodward derailed the train to free it from captivity.
Colonel Nelec and his men storm the school and capture the boys. They place the children on a security bus and head back to the Air Force base, but the alien attacks the bus on the way. Nelec and his men are killed, while Joe and his friends escape. The kids head through the town, which is now under heavy fire from malfunctioning military equipment as the military attempts to battle the alien. They find the alien's subterranean lair near the cemetery where Joe's mother is buried, along with several missing people who have been trapped there by the alien, which has apparently kept them for food. The town's missing electronics are there too, formed together to create a giant electromagnet underneath the base of the water tower. Joe manages to rescue Alice, but, as they escape, the alien grabs Joe, who tells the creature that it can still live on even after painful events. The alien understands Joe's meaning through their tactile telepathic connection and lets go of him, allowing him and his friends to escape.
Shortly after, all the cubes (which break free from Air Force transport trucks) as well as loose metal from around the town are attracted to the town's water tower. The cubes begin to align and a ship begins to take form around the water tower, which the alien then enters. Joe's metal locket, which contains a picture of him as a baby with his mother, is also drawn towards the tower, and, after a moment, he decides to let it go, finally putting the past behind him. Everyone watches as the ship takes off toward space.During the end credits, the full movie that Charles and his friends were working on, titled The Case, is shown, with an epilogue in which Charles asks the film festival judges to select his movie, before he is assaulted by a zombie played by Alice.