The show follows the adventures of the core Beast Wars cast upon their return home to Cybertron; there, Optimus Primal and his crew find that the whole planet is abandoned, and the streets are patrolled by mindless Vehicon drones serving Megatron, who somehow escaped his captivity.
Worse still, they learn that they are infected with a deadly virus that will kill them in a matter of hours. Salvation comes from the mysterious supercomputer known as the Oracle, who sees them fit to complete its mission of a planetwide "reformatting", and turns them into technorganic warriors, a perfect blend of organic and technological matter.
As the show progresses, Primal and his fellow Maximals learn to balance their technological side with their newly introduced organic aspects, mastery coming in slow stages. Unlike the previous conflict, where sides had been roughly equal, the four original Maximals were quite outnumbered by their Vehicon enemies, and the battles took on a "guerilla warfare" feel, with the Maximals using sewers and underground levels to their advantage and avoiding surface levels unless for combat purposes. As the show progresses, two brand-new Maximals and a returning face boost their numbers.
Initially, Optimus is driven by a crusade to restore the organic above the technological and to right his failure to stop Megatron. Over time, it becomes increasingly clear that he's becoming obsessed and overzealous. At the midpoint, after Cybertron is almost destroyed, he realises that the point should be to create a balance of organic and technological, not a supremacy. Under this new, saner cause, the Maximals eventually turn Cybertron into an technorganic paradise, though at the cost of their leader's life.