A fire starts aboard the Colonial Marine spaceship Sulaco. The computer launches an escape pod containing Ellen Ripley, the young girl Newt, Hicks, and the damaged android Bishop; all four are in cryonic stasis. Scans of the crew's cryotubesshow an Alien facehugger attached to one member. The pod crash-lands on Fiorina "Fury" 161, a foundry facility and penal colony inhabited by male inmates with double-Y chromosome syndrome, a genetic mutation present in some males in the 22nd century which gives the afflicted individual a predisposition for brutal antisocial behavior such as rape and murder. The inmates, who live and work on Fiorina "Fury" 161 due to their dangerous nature and histories of violence, recover the crashed pod and its passengers. Another facehugger is seen approaching an inmate's dog, Spike.
Ripley is awakened by Clemens, the prison doctor, who informs her that she is the sole survivor. She is warned by the prison warden, Harold Andrews, that her presence may have disruptive effects. Ripley insists that Clemens perform an autopsy on Newt, secretly fearing that Newt may be carrying an Alien embryo. Despite protests from the warden and his assistant Aaron, the autopsy is conducted and no embryo is found.
Elsewhere in the prison, a quadrupedal alien bursts from Spike. Growing to full size, the Alien kills several members of the colony and returns outcast prisoner Golic to his previously psychopathic state. Ripley finds the damaged Bishop in the wreckage of the ship. Just as she is leaving the wreckage, four of the inmates attempt to rape her, but Dillon intervenes and hits the inmates with a crowbar. Ripley heads back to the infirmary, and re-activates Bishop, who confirms that a facehugger came with them to Fiorina in the escape pod. Ripley informs Andrews of her encounters with the Aliens and suggests everyone work together to hunt down and kill it. Andrews does not believe her story, but explains that the facility has no weapons; their only hope is the rescue ship being sent for Ripley by the Weyland-Yutani Corporation.
The Alien surprises Ripley and Clemens in the prison infirmary, where it kills Clemens. It examines Ripley, but spares her and retreats. Andrews orders Aaron to take her back to the infirmary, but he is ambushed and killed by the Alien. Ripley rallies the inmates and proposes they pour flammable toxic waste into the ventilation system and ignite it to flush out the Alien. However, the Alien's intervention causes an explosion and several inmates are killed. With Aaron's help, Ripley, scans herself using the escape pod's medical equipment and discovers the embryo of an Alien Queen growing inside her. She also discovers that Weyland-Yutani hopes to turn the Aliens into biological weapons.
Deducing that the Alien will not kill her because of the embryo she carries, Ripley begs Dillon to kill her; he agrees only if she helps the inmates kill the adult creature first. They form a plan to lure the creature into the foundry's molding facility, trap it via a series of closing doors, and drown it in molten lead. The bait-and-chase plan results in the death of every prisoner except Morse and Dillon. Dillon remains in the mold to distract the Alien, allowing it to tear him apart as Morse pours the molten lead onto them. The Alien is covered in molten metal but escapes the mold; Ripley activates the fire sprinklers, causing the Alien's exoskeleton to cool rapidly and shatter, killing it.
The Weyland–Yutani commando team arrives, including a man who looks identical to Bishop, who explains that he is Bishop's creator. He tries to persuade Ripley to undergo surgery to remove the Queen embryo, which he claims will be destroyed. Ripley refuses and steps back onto a mobile platform, which Morse positions over the furnace. The Weyland–Yutani team shoot Morse in the leg in a late effort to stop him; Aaron strikes a team member with a wrench and is shot dead. Ignoring the commandos' pleas, Ripley throws herself into the furnace as the infant Alien Queen erupts from her chest. Ripley grabs it to prevent it from escaping as they both fall into the furnace. The facility is closed and the only surviving inmate, Morse, is led away.
- Knockout, Dolphy, Puffer, Rachel, Mighty Joe, Daylight, Jenny, Pete, Kevin, Blythe Baxter, Zoe Trent, Pepper Clark, Penny Ling, Vinnie Terrio, Sunil Nevla, Minka Mark, and Russell Ferguson guest star in this film.
- The storyline concludes in Thomas and Twilight Sparkle's Adventures of Alien: Resurrection.