In Los Angeles, November 2019, retired police officer Rick Deckard (Harrison Ford) is detained by officer Gaff (Edward James Olmos) and brought to his former supervisor, Bryant (M. Emmet Walsh). Deckard, whose job as a "Blade Runner" was to track down bioengineered beings known as replicants and destroy them, is informed that four have come to Earth illegally. As Tyrell Corporation Nexus-6 models, they have only a four-year lifespan and may have come to Earth to try to extend their lives.
Deckard watches a video of a Blade Runner named Holden administering the "Voight-Kampff" test designed to distinguish replicants from humans based on their emotional response to questions. The test subject, Leon (Brion James), shoots Holden after Holden asks about Leon's mother. Bryant wants Deckard to retire Leon and the other replicants: Roy Batty (Rutger Hauer), Zhora (Joanna Cassidy), and Pris (Daryl Hannah). Deckard initially refuses, but after Bryant ambiguously threatens him, he reluctantly agrees.
Deckard begins his investigation at the Tyrell Corporation to ensure that the test works on Nexus-6 models. While there, he discovers that Dr. Eldon Tyrell's (Joe Turkel) assistant Rachael (Sean Young) is an experimental replicant who believes herself to be human. Rachael has been given false memories to provide an "emotional cushion". As a result, a more extensive test is required to determine whether she is a replicant.
Events are then set into motion that pit Deckard's search for the replicants against their search for Tyrell to force him to extend their lives. Roy and Leon investigate a replicant eye-manufacturing laboratory and learn of J.F. Sebastian (William Sanderson), a gifted designer who works closely with Tyrell. Rachael visits Deckard at his apartment to prove her humanity by showing him a family photo, but after Deckard reveals that her memories are only implants taken from a real person, she leaves his apartment in tears. Meanwhile, Pris locates Sebastian and manipulates him to gain his trust.
While searching Leon's hotel room, Deckard finds a photo of Zhora and a synthetic snake scale that leads him to a strip club where Zhora works. Deckard kills Zhora and shortly after is told by Bryant to also kill Rachael, who has absconded from the Tyrell Corporation. Deckard spots Rachael in a crowd but is attacked by Leon. Rachael kills Leon using Deckard's gun, and the two return to Deckard's apartment, where he promises not to hunt her. Later they share an intimate moment; Rachael abruptly tries to leave, but Deckard physically restrains her and forces Rachael to kiss him.
Arriving at Sebastian's apartment, Roy tells Pris the others are dead. Sympathetic to their plight, Sebastian reveals that because of "Methuselah Syndrome", a genetic premature aging disorder, his life will also be cut short. Sebastian and Roy gain entrance into Tyrell's secure penthouse, where Roy demands more life from his maker. Tyrell tells him that it is impossible. Roy confesses that he has done "questionable things" which Tyrell dismisses, praising Roy's advanced design and accomplishments in his short life. Roy kisses Tyrell, then kills him. Sebastian runs for the elevator followed by Roy, who then rides the elevator down alone.
Upon entering Sebastian's apartment, Deckard is ambushed by Pris, but manages to kill her just as Roy returns. As Roy's body begins to shut down, he chases Deckard through the building and ends up on the roof. Deckard tries to jump to another roof, but misses and is left hanging precariously between the buildings. Roy makes the jump with ease, and as Deckard's grip loosens, Roy hoists him onto the roof, saving him. As his life runs out, Roy delivers a monologue about how his memories are about to be lost; Roy dies in front of Deckard, who watches silently. Gaff arrives and shouts to Deckard, "It's too bad she won't live, but then again, who does?" Deckard returns to his apartment to find Rachael sleeping in his bed. As they leave, Deckard finds a small tin-foil origami unicorn, a calling card left by Gaff. Depending on the version, Deckard and Rachael either leave the apartment block to an uncertain future, or drive through an idyllic pastoral landscape.