Upon the insistence of Rose, his Caucasian girlfriend, Chris Washington, an African-American photographer, hesitantly concedes to meet her parents and spend the weekend at their country estate. En route, they hit a deer and report the incident to the police. The investigating officer accusingly asks for Chris’s ID, even though it was Rose at the wheel at the time of the impact. Rose vehemently protests and the officer backs off promptly. The incident is brushed off as a minor road mishap.
Once they arrive at the Armitage country estate, Chris notices the presence of an African American groundskeeper and housekeeper and is bothered by the sight, but Rose reassures him. Soon, Chris is warmly received by Rose’s parents—Dean, an accomplished neurosurgeon, and Missy, a hypnotherapist. Dean takes Chris for a tour of the estate and makes a couple of mildly questionable comments concerning race relations but quickly smoothes things over. Before dinner, Jeremy, Rose’s younger brother, arrives. Jeremy makes a number of off-putting remarks about African Americans and asks Chris to allow him to demonstrate some jiu-jitsu moves on him, but Missy soon diffuses the situation.
Later that evening Chris finds it difficult to sleep so he goes outside to smoke and sees Walter, the Armitages' groundskeeper, sprinting full throttle in the dead of night, oblivious to his presence. Georgina, their maid, also acts strangely, prowling around the house like a ghost. Chris, upon seeing all this strangeness, decides to call it a night, but is caught by Missy who forces him to undergo a hypnotherapy session intended to “cure” him of his smoking habit. Despite Chris's reluctance, Missy manages to put him into a deep trance where he recalls his mother’s death as a child. Upon discovering Chris's guilty feelings concerning his mother’s death, Missy leverages these feelings to sink Chris’s consciousness within a dark void within his unconsciousness, a place she calls “The Sunken Place.”
When Chris awakens from the trance, he finds himself in bed once more, covered in sweat. Initially, he dismisses the whole thing as a dream, but realizes that it was indeed real as cigarettes now nauseate him. Walter then confirms that he had indeed gone through a hypnotherapy session and was with Missy for quite some time. The strange interactions with Walter and Georgina continue, but Chris just tries to shrug it off.
Not too long afterward, throngs of wealthy Caucasian guests begin to arrive at the Armitage estate for their fancy annual party. These guests take a keen interest in Chris, but in a very peculiar manner—either admiring his physique as if he were livestock, or making other unusual comments about African American people in his presence. Looking for respite from all the bizarreness, he breaks away from the crowd where he meets Jim Hudson, an art dealer whom he admires. Ironically, Jim is blind, but he takes particular interest in Chris’ work as a photographer.
After recovering somewhat he returns to the party where he meets another African American man who introduces himself as Logan King. Logan, despite his youth, is dressed in a manner more appropriate to a man several times his senior. His behavior is likewise off; he responds to everything in a mechanical, almost rehearsed manner. Even more puzzling is his choice of wife: a heavy-set, Caucasian woman, about three decades his senior. Despite not having met Logan before, Chris is reminded of someone he once knew and decides to discreetly take a photo of him to send to his friend Rod Williams, a Transportation Security Agent. His flash goes off, triggering an even stranger reaction from Logan, causing his nose to bleed and sending him into a hysterical frenzy. He begins pushing Chris in a panicked manner, ordering him to “get out!”
The other guests quickly restrain him while their hosts attempt to calm him down. Logan eventually regains his composure after a quick session with Missy and he apologizes to the guests, explaining that he had an epileptic seizure which caused him to freak out. Chris, properly spooked by all the weirdness he experiences, finally manages to convince Rose that they need to leave. Unknown to Chris, however, as he and Rose discuss their next steps the guests of the Armitage family are holding an auction with Chris as the prize. Jim Hudson wins the bidding and Dean goes into action to prep his prize. Meanwhile, Chris manages to send Logan’s photo to Rod, who recognizes Logan. His real identity is Andre Hayworth, and he has apparently been missing for half a year already. Rod reports the missing men to the police but they ridicule him rather than help him.
While preparing to escape, Chris finds a small cabinet with a box full of photos of Rose posing with various black people—including one of Georgina. This is Rose’s collection of previous “acquisitions.” Chris realizes how bad his situation is, but it's now too late—the entire Armitage family prevents him from leaving the house. Rose finally drops her ruse, telling him that everything she had done—the concern, the intimacy, everything—was intended to lure him in. Missy uses a hypnotic keyword to render him cataleptic. When he comes to, he finds himself strapped to a leather chair in the basement game room in front of a TV set playing a dated video of Rose’s grandfather, Roman.
Roman divulges the horrible truth behind the abductions: they are done so that wealthy Caucasian patrons can use strong, healthy, young African American bodies to serve as hosts for them, via a combination of complex neurosurgery and hypnotic conditioning. The host body’s consciousness remains deep within “The Sunken Place” as a helpless participant, essentially trapped within one's own self. The screen suddenly switches from Roman to Jim Hudson. Jim tells Chris that he bid on him so that he can get a new set of eyes—as well as Chris’ unique artistic abilities.
Chris manages to save himself by stuffing his ears with the stuffing of the chair to which he is strapped, blocking out the hypnotic suggestions. He manages to kill both Jeremy and Dean when they try to ready him for surgery. He is about to escape in Jeremy’s car when he hits Georgina. Wracked with guilt from newly liberated childhood memories, he carries Georgina to bring her to safety but is horrified to discover that she had also undergone a brain-switch procedure. Georgina is in fact Marianne, Rose’s grandmother. She begins to savagely beat Chris causing them to crash into a tree, killing her and temporarily stunning Chris, which gives Rose time to locate him.
With Rose is Walter—who in fact is Roman, Rose's grandfather and the founder of the “Order of the Coagula” a clandestine cult of sorts dedicated to making brain-switches for their wealthy patrons. Walter attacks Chris, but Chris manages to break Walter’s hypnotic trance by using his phone camera’s flash. Awakened at last, Walter then turns on Rose then tragically turns the rifle on himself. A critically injured Rose tries to shoot Chris but fails. Chris starts to strangle her in retribution but decides against killing her. A police siren sounds in the distance, spelling certain doom for Chris—but as it turns out, it's Rod, Chris's best friend, who has arrived in time to rescue his friend. They leave together as Rose bleeds to death on the driveway of the Armitage estate.
