In the year 2071, roughly fifty years after an accident with a hyperspace gateway that made Earth almost uninhabitable, humanity has colonized most of the rocky planets and moons of the Solar System. Amid a rising crime rate, the Inter Solar System Police (ISSP) set up a legalized contract system, in which registered bounty hunters (also referred to as "Cowboys") chase criminals and bring them in alive in return for a reward. The series' protagonists are bounty-hunters working from the spaceship Bebop. The original crew is Spike Spiegel, an exiled former hitman of the criminal Red Dragon Syndicate, and Jet Black, a former ISSP officer. They are later joined by Faye Valentine, an amnesiac con artist; Edward, an eccentric child, skilled in hacking; and Ein, a genetically-engineered Pembroke Welsh Corgi with human-like intelligence. Throughout the series, the team gets involved in disastrous mishaps leaving them without money, while often confronting faces and events from their past: These include Jet's reasons for leaving the ISSP and Faye's past as a young woman from Earth injured in an accident and cryogenically frozen to save her life.

While much of the show is episodic, the main story arc focuses on Spike and his deadly rivalry with Vicious, an ambitious criminal affiliated with the Red Dragon Syndicate. Spike and Vicious were once partners and friends. Still, when Spike begins an affair with Vicious's girlfriend Julia and resolves to leave the Syndicate with her, Vicious seeks to eliminate Spike by blackmailing Julia into killing him. Julia hides to protect herself and Spike, while Spike fakes his death to escape the Syndicate. In the present, Julia comes out of hiding and reunites with Spike, intending to complete their plan. Vicious, having staged a coup d'état and taken over the Syndicate, sends hitmen after the pair. Julia is killed, leaving Spike alone. Spike leaves the Bebop after finally apologizing to Faye and Jet. Upon infiltrating the syndicate, he finds Vicious on the top floor of the building and confronts him after dispatching the remaining Red Dragon members. The final battle ends with Spike killing Vicious, only to be seriously wounded himself in the ensuing confrontation. Looking up to the sky, Spike sees Julia. The series concludes as Spike descends the main staircase of the building into the rising sun before eventually falling to the ground.