In the future, the human race has been assimilated by benevolent extraterrestrial psychic parasites called "Souls". Melanie Stryder (Saoirse Ronan), a human, is captured by the Seeker (Diane Kruger) and infused with a soul called "Wanderer ", in order to discover the location of one of the last pockets of non-assimilated humans. However, Melanie survives the procedure and begins to struggle for control of her body.
Wanderer discovers that Melanie was captured while scavenging for food with her brother Jamie Stryder (Chandler Canterbury) and her boyfriend Jared Howe (Max Irons), and that they were looking for Melanie's uncle Jeb Stryder (William Hurt), who lives in a cabin in the desert. Wanderer loses control of Melanie and the Seeker decides to put Wanderer in a different body and be insterted into Melanie to get the information herself. With the help of Melanie, Wanderer escapes and makes her way to the desert, eventually found by a group of humans, including Jeb. She is taken to a series of underground caves, discovering that Jared and Jamie are living there too.
Wanderer is kept isolated from the others, eventually interacting with the humans, and develops feelings for one of them, Ian O'Shea (Jake Abel), beginning to believe the Souls shouldn't steal other people's free will. Eventually, Jeb, Jamie and Ian realize Melanie is still alive, while The Seeker learns that the community is located somewhere in the desert and follows Wanderer there, but fails to locate them. After nearly being captured by the Seeker, Ian's brother Kyle O'Shea (Boyd Holbrook) attempts to kill Wanderer, but is stopped by Ian and another human, Wes, after which Jared also learns that Melanie is still alive.
Wanderer is horrified to learn that Doc (Scott Lawrence), the community's medic, has been experimenting on people infused with Souls, removing the Souls from their bodies and killing them, and isolates herself from the group, but agrees to help Jared infiltrate a Soul medical facility to steal technology to cure the ill Jamie. In the process, they are attacked by the Seeker, who is then shot and captured by Jeb. The Seeker is taken to the caves, where she is removed from her host and contained in a pod stolen by Wanderer, who then sends the Seeker to a distant planet.
Wanderer teaches Doc how to remove the Souls from people's bodies without harming them, and asks to be removed from Melanie's so Melanie can have her life back. Melanie protests, having bonded with Wanderer, but Doc goes through with the procedure. However, rather than letting Wanderer die, Doc inserts her into Pet (Emily Browning), a human who was left brain-dead after the Soul inside her was removed. Wanderer, now in Pet's body, begins a relationship with Ian, while Melanie reunites with Jared. A few months later, Wanderer and the others meet another group of humans who have been joined by a Soul, Burns, who also decided to live peacefully among them.