Alien Resurrection takes place 200 years after Alien 3. Ellen Ripley (Sigourney Weaver) has been cloned on the outer space military science vessel USM Auriga using "blood samples from Fury 16, on ice." The United Systems Military wants to extract the Alien queen embryo that was implanted in her before her death in Alien 3. After successful extraction of the embryo, the scientists decide to keep the Ripley clone alive for further study. They raise the Alien queen and collect her eggs for further use. As a result of the cloning process, during which Ripley's DNA was mixed with the Alien's, she has developed abilities including enhanced strength and reflexes, acidic blood, and an empathic link with the Aliens.


The Betty, a ship full of mercenaries, arrives delivering several kidnapped humans in hypersleep. The military scientists use them as hosts for the Alien facehuggers, raising several adult Aliens for study. The mercenaries encounter Ripley, and their youngest member Call (Winona Ryder) recognizes her name. She attempts to kill Ripley, believing she may be used to create more Aliens. Call is too late; the adult Aliens have already been created and quickly escape their confinement, damaging the ship and killing most of its crew. Dr. Wren (J. E. Freeman), one of the ship's scientists, reveals that the Auriga's default command in an emergency situation is to return to Earth. Realizing that this will unleash the Aliens on Earth, Ripley, the mercenaries, Wren, a marine named DiStephano (Raymond Cruz), and a surviving Alien host, Purvis (Leland Orser), attempt to escape on the Betty and destroy the Auriga.


As the group makes their way through the damaged ship several of them are killed by the Aliens. Call is revealed to be an android after Wren betrays the group. Using her abilities to interface with the damaged ship's systems, they set it on a collision course with Earth, hoping that the Aliens will be destroyed in the crash. Ripley learns that the Alien queen has gained a human ability from her DNA as well: it has grown a womb and can give birth to live offspring without the need for eggs and human hosts. The resulting offspring, which is a mixture of human and Alien traits, recognizes Ripley as its "mother" and kills the Alien queen.


Ripley and the surviving mercenaries arrive at the Betty. As they launch, the human/Alien hybrid attacks Ripley and Call. Ripley kills it by using her own acidic blood to burn a hole through a viewing pane, causing the creature to be drawn violently through the small hole and into the vacuum of space. The survivors escape in the Betty as the Auriga impacts into Earth.