A black man named Andre Hayworth is wandering around a suburban neighborhood lost. He is followed and abducted by another man in a white Porsche.
Chris Washington, a black photographer living in Brooklyn, is packing for a road trip to meet the family of his white girlfriend, Rose Armitage. He nervously asks Rose if her family knows about their interracial relationship, but she assures him that they are not racist. He makes sure he’s the only black guy Rose has ever dated. She says he is, but is confident that her parents will be totally cool.
On the ride over, Chris calls his best friend Rod, a TSA agent, who is watching over his dog. A deer runs out into the road and gets hit. When a cop arrives, he asks to see Chris's ID, but when Rose insists there's no reason to do that since Chris wasn't driving, the cop lets them go.
Chris and Rose arrive at her parents’ home. Her dad, Dean Armitage is an neurosurgeon who says he would have voted for Obama a third time if he could have. Her mom, Missy, is a hypnotherapist. She offers to cure Chris of his nicotine addiction through hypnosis, but he doesn’t feel cool with people tooling around in his head. The Armitages have two black helpers, a groundskeeper named Walter and a maid named Georgina.
Dean gives Chris a tour of the house and shows him old family photos. His father Roman was beat out by Jesse Owens to compete in the Olympics in front of Hitler. And while that was sad for his dad, it was still great to have Hitler’s Aryan idealism proven wrong. He taps on the basement door and says it's closed off due to black mold. The family gets together for afternoon tea. Missy asks about Chris’s parents. His dad left when he was young and his mom was hit by a car when he was eleven. Rose's brother Jeremy arrives.
In the middle of the night, Chris sneaks out for a cigarette, and sees Walter running towards him before making a sharp turn. Inside the house, Georgina is staring out a window. It turns out she’s looking at her own reflection, not Chris. When Chris goes back inside, Missy pressures him into a hypnotherapy session to cure his smoking addiction. He admits he feels responsible for his mother's death since he waited too long to call for help and just watched TV. He then enters a void Missy calls the "Sunken Place." His consciousness has left his body, while his body is still paralyzed in his chair.
Chris wakes up in his bed. He assumes the whole thing was a dream until Walter apologizes for running at him last night. However, he is pleased to discover that the hypnosis was a success, as he no longer feels a desire to smoke. He plugs his cell phone into a battery recharger.
Dozens of wealthy white people arrive for the Armitages' annual get-together, expressing admiration for Chris's physique. Jim Hudson, an art dealer who has gone blind in his old age, takes a particular interest in Chris's photography skills. Chris meets another black man, Logan King, who acts as strange as Walter and Georgina and who's married to a much older white woman.
When Chris goes to get his phone, he finds it's been unplugged. He takes a picture of Logan, who suddenly starts acting hysterical after the camera flash. His nose starts bleeding and he yells at Chris to "get out" repeatedly before Jeremy restrains him. Dean claims the camera flash caused him to have a seizure, and Logan apologizes for how he acted.
Chris and Rose go for a walk and Chris tells her that he’s sure he recognizes the guy and that something strange is definitely going on. They talk out by the lake about his mother's death and how he would never abandon her. Chris says that he’d really like to go home now. Rose reluctantly agrees. She says she’ll make up something to tell her parents. Meanwhile, the party guests hold a silent auction, disguised as a game of bingo with Chris as the "prize." Jim makes the winning bid.
Chris sends the photo of Logan to Rod, who recognizes him as Andre Hayworth. Suspecting a conspiracy, Rod tells Chris to get out of there just as Chris's battery dies. While Chris packs to leave, he finds a red box in Rose's closet containing photos of Rose in prior relationships with several black partners, including Walter and Georgina, contradicting her earlier claim that Chris is the first black person she has dated. Chris goes downstairs to try to leave as Dean, Missy and Jeremy surround him. He asks Rose where are the keys. Rose searches around her purse for them before revealing she can't let him have them. Missy uses a hypnotic trigger to knock Chris out, sending him to the Sunken Place.
Rod tries to tell the police his theory about black people being abducted and brainwashed, but they laugh him out of the office. Chris wakes up tied to a chair in the basement and watches a video where Roman explains that the family transplants white people's brains into others' bodies, granting them preferred physical characteristics and immortality. Rod tries Chris’s phone again and Rose answers. She says that Chris left two days ago. He starts to realize that she's lying, so he tries to record the call. Rose nullifies the recording by trying to act like Rod was always attracted to her.
Chris then speaks with Jim through an intercom. Jim explains that they're going to swap brains and Chris will only continue existing in the dark void as a passenger. When Chris asks why they target black people, Jim shrugs and tries to insist he isn't interested in Chris for his race but rather his photographic eyes. Chris sees that his finger nails have clawed through the leather arm of the chair and exposed the padding.
Missy activates the hypnotic trigger to knock Chris out again. Jeremy unties Chris for the surgery, but Chris blocked the hypnotic trigger by plugging his ears with cotton stuffing pulled from the chair. Chris bludgeons Jeremy with a bocce ball and impales Dean with the antlers of a deer mount, knocking over a candle which sets fire to the operating room with an anesthetized Jim inside. Missy attacks Chris in the kitchen, but he stabs and kills her. Jeremy attacks him again as he heads for the door, but Chris kills him too. On the way out, he hits Georgina (possessed by Rose's grandmother, Marianne) and knocks her unconscious. Compelled by guilt from his mother's death, he decides to carry her into the car, but she awakens and attacks him. In the ensuing struggle, the car crashes into a tree and Georgina/Marianne is killed.
Rose and Walter (possessed by Roman) arrive and hold Chris at gunpoint. Chris uses the flash on his phone to incapacitate Roman. Walter temporarily regains control of his body, taking Rose's rifle and shooting both her and himself. Chris begins to strangle the wounded Rose, but he finds himself unable to kill her. Police sirens approach, and Rose cries out for help, but the driver is revealed to be Rod. He drives away with Chris, leaving Rose to bleed out on the road.
