In 2019 Los Angeles, former police officer Rick Deckard is detained by Officer Gaff, who likes to make origami figures, and is brought to his former supervisor, Bryant. Deckard, whose job as a "blade runner" was to track down bioengineered humanoids known as replicants and terminally "retire" them, is informed that four replicants are on Earth illegally. Deckard begins to leave, but Bryant ambiguously threatens him and Deckard stays. The two watch a video of a blade runner named Holden administering the Voight-Kampff test, which is designed to distinguish replicants from humans based on their emotional responses to questions. The test subject, Leon, shoots Holden on the second question. Bryant wants Deckard to retire Leon and three other Nexus-6 replicants: Roy Batty, Zhora, and Pris.
Bryant has Deckard meet with the CEO of the company that creates the replicants, Eldon Tyrell, so he can administer the test on a Nexus-6 to see if it works. Tyrell expresses his interest in seeing the test fail first and asks him to administer it on his assistant Rachael. After a much longer than standard test, Deckard concludes privately to Tyrell that Rachael is a replicant who believes she is human. Tyrell explains that she is an experiment who has been given false memories to provide an "emotional cushion", and that she has no knowledge of her true nature.
In searching Leon's hotel room, Deckard finds photos and a scale from the skin of an animal, which is later identified as a synthetic snake scale. Deckard returns to his apartment where Rachael is waiting. She tries to prove her humanity by showing him a family photo, but Deckard reveals that her memories are implants from Tyrell's niece, and she leaves in tears.
Replicants Roy and Leon meanwhile investigate a replicant eye-manufacturing laboratory and learn of J. F. Sebastian, a gifted genetic designer who works closely with Tyrell. Pris locates Sebastian and manipulates him to gain his trust.
A photograph from Leon's apartment and the snake scale lead Deckard to a strip club, where Zhora works. After a confrontation and chase, Deckard kills Zhora. Bryant also orders him to retire Rachael, who has disappeared from the Tyrell Corporation. Deckard spots Rachael in a crowd, but he is ambushed by Leon, who knocks the gun out of Deckard's hand and beats him. As Leon is about to kill Deckard, Rachael saves him by using Deckard's gun to kill Leon. They return to Deckard's apartment and, during a discussion, he promises not to track her down. As Rachael abruptly tries to leave, Deckard restrains her and forces her to kiss him, and she ultimately relents. Deckard leaves Rachael at his apartment and departs to search for the remaining replicants.
Roy arrives at Sebastian's apartment and tells Pris that the other replicants are dead. Sebastian reveals that because of a genetic premature aging disorder, his life will be cut short, like the replicants that were built with a four-year lifespan. Roy uses Sebastian to gain entrance to Tyrell's penthouse. He demands more life from his maker, which Tyrell says is impossible. Roy confesses that he has done "questionable things" but Tyrell dismisses this, praising Roy's advanced design and accomplishments in his short life. Roy kisses Tyrell and then kills him by crushing his skull. Sebastian tries to flee and is later reported dead.
At Sebastian's apartment, Deckard is ambushed by Pris, but he kills her as Roy returns. Roy's body begins to fail as the end of his lifespan nears. He chases Deckard through the building and onto the roof. Deckard tries to jump onto another roof but is left hanging on the edge. Roy makes the jump with ease and, as Deckard's grip loosens, Roy hoists him onto the roof to save him. Before Roy dies, he laments that his memories "will be lost in time, like tears in rain". Gaff arrives to congratulate Deckard, also reminding him that Rachael will not live, but "then again, who does?" Deckard returns to his apartment to retrieve Rachael. While escorting her to the elevator, he notices a small origami unicorn on the floor. He recalls Gaff's words and departs with Rachael.