In a distant part of the galaxy lie The Twelve Colonies of Man, a civilization that has been at peace for some forty years with an empire of machines, the Cylons, who were created generations before as worker drones for mankind, but became independent, rose in rebellion, and launched war on their masters. Now, the Cylons have evolved into more human form, into machine-created biological beings, who seek to exterminate true biological humans. To this end they use a human scientist, Gaius, to help one of their infiltrators, known as #6, penetrate the Colonies' master defense mainframes; Gaius is reluctant but smitten by #6, a Cylon woman of seemingly insatiable sexual desire, and the result of their affair is a nuclear sneak-attack that obliterates the Colonies and the star navy deployed for their protection. One ship, however, survives, an obsolete battlestar known as the Galactica; scheduled for decommissioning, the Galactica instead must lead 50,000 surviving humans on a quest for a new home world, where they must bear children to rebuild their race. First, however, the Galactica must lead surviving ships of the Colonies to a weapons deployment base within a spatial storm, a rendezvous that leaves them trapped when two Cylon base stars track them down and open fire.

After forty years of armistice, the Cylons attacks the Twelve Colonies of Kobol. Their strategy: a virus implanted into the mankind defense system. The former Battlestar Galactica, which is being adapted into a museum, is not connected with the defense system and becomes the only warship capable of fighting against the Cylons in the hopes of leading the survivors to planet 'Earth'.