In the 26th century, humanity has left an overpopulated Earth to colonize a new solar system. The central planets formed the Alliance and won a war against the outer planet Independents those refusing to join the Alliance. River Tam (Summer Glau) is coercively conditioned by Alliance scientists into a psychic assassin. She is rescued by her brother Simon (Sean Maher). During her training, River inadvertently read the minds of several officers and learned top government secrets. Consequently, a top Alliance agent known only as the Operative (Chiwetel Ejiofor) is tasked with recapturing her.
The siblings have found refuge aboard the transport spaceship Serenity with Captain Malcolm "Mal" Reynolds (Nathan Fillion), first mate Zoe Washburne (Gina Torres), pilot Hoban "Wash" Washburne (Alan Tudyk), mercenary Jayne Cobb (Adam Baldwin), and mechanic Kaylee Frye (Jewel Staite). Despite Simon's objections, Mal brings River on a bank robbery where they are attacked by savage and cannibalistic Reavers. They escape, but Simon decides he and River will leave Serenity at the next port. Once there, however, a television commercial causes River to attack numerous bar patrons, and Mal takes the siblings back aboard the ship. The crew contacts reclusive hacker Mr. Universe (David Krumholtz), who discovers a subliminal message designed to trigger River's mental conditioning. He notes River whispered "Miranda" before attacking and warns that someone else saw the footage.
Mal is invited to visit Inara Serra (Morena Baccarin), a former Serenity occupant. Despite knowing she is held hostage as a trap, Mal goes to rescue her. The Operative confronts Mal, promising to let him go free if he turns over River. Mal refuses and escapes with Inara. River reveals that Miranda is a planet located beyond a region of space swarming with Reavers. The crew flies to the planet Haven to ponder their next move. They find Haven devastated and their old friend, Shepherd Book (Ron Glass), mortally wounded. The Operative claims responsibility for the killings. He promises to keep pursuing them and killing anyone who assists them until he captures River.
Despite the crew's objection, Mal disguises Serenity as a Reaver ship and travels to Miranda. On the planet, the crew find all its colonists dead and a recording by the last surviving member of an Alliance survey team (Sarah Paulson). She explains that an experimental chemical designed to suppress aggression was added into Miranda's air. Most residents became so docile they stopped performing all activities of daily living and allowed themselves to die. A small portion of the population had the opposite reaction and became exceedingly aggressive and violent, turning into Reavers.
Mr. Universe agrees to broadcast the recording, luring the crew to the Operative. However, the Operative mortally wounds him, destroys his transmitting equipment, and prepares an ambush. Though Mal suspects a trap, he must deliver broadcast the recording. On the way, they provoke the Reaver fleet into pursuing them. While the Reaver fleet clashes with the waiting Alliance fleet, Serenity crash lands near the broadcast tower. Wash is killed by Reavers shortly after.
The crew make a last stand against the Reavers to buy Mal time to broadcast the recording. Through a message recorded by Mr. Universe before his death, Mal learns of a backup transmitter. Sustaining heavy injuries, the crew retreats behind a set of blast doors that fail to properly close. A Reaver shoots through the opening and severely wounds Simon, prompting River to dive through the doors and close them as the Reavers drag her away. At the backup transmitter, Mal incapacitates the Operative and forces him to watch the broadcast recording. Mal returns to the crew, and the blast doors open to reveal that River has killed all the Reavers. Alliance troops reach the group, but the Operative orders them to stand down.
The Operative provides medical aid and resources to repair Serenity. The Operative tells Mal the broadcast has weakened the Alliance government. While he will try to convince the Parliament that River and Simon are no longer threats, he cannot guarantee the Alliance will end their pursuit. Serenity takes off with River as Mal's co-pilot.
Output: Who kills Mr. Universe?