In the season one pilot, “Darkness Rising”, Cliffjumper is murdered by Starscream. His corpse is used by Megatron to test thenecromanticDark Energon, to create anundeadarmy from Cybertron’s fallen. The plan fails when the Autobots destroy Megatron’s space bridge, leaving him in acomatosestate. He eventually recovers and takes back his leadership role from the treacherous Starscream, who later defects to follow his own path. In the season one finale, the Autobots and Megatron join forces to prevent the rise of Unicron. Optimus uses theMatrix of Leadershipto knock Unicron back into hibernation, but in doing so, loses his memories and regains his pre-war personality of Orion Pax.
In season two, Megatron manipulates the amnesiac Optimus into decrypting the Iacon archives, which contain the coordinates to Cybertronian relics hidden on Earth. Jack travels to Cybertron, obtaining Optimus’ memories from Vector Sigma, and restores them to Optimus, via the Matrix of Leadership. The season is based mostly around the hunt for the Iacon relics. Starscream obtains the four Omega Keys, which power the Omega Lock, a device which can reboot the dead Cybertron. He gives them to Megatron in return for clemency. Optimus destroys the Omega Lock, but not before Megatron uses its powers to create a new base on Earth – Darkmount. The Decepticons then target and destroy the Autobot base, unaware the team escaped beforehand using their ground bridge.
The third season, subtitled "Beast Hunters", begins with the reunification of Team Prime, introducing Ultra Magnus as Optimus' second-in-command. The Autobots successfully destroy Darkmount. Shockwave arrives on Earth, planning to create an army of Predacons, starting with Predaking. But when Predaking shows intelligence, Megatron has Shockwave terminate his project, pinning its destruction on the Autobots. Soundwave later kidnaps Ratchet. Megatron forces him to rebuild the Omega Lock using synthetic Energon. Ratchet informs Predaking of the truth, and he defects. During the battle for the Omega Lock, Bumblebee is shot by Megatron, falling into the synthetic Energon. However, he survives, gaining a healed voice, and runs Megatron through with the Star Saber, killing the Decepticon leader. The Autobots use the Omega Lock to restore Cybertron and head home victorious.
The series ends with the television movie,Predacons Rising, where the Autobots and remaining Decepticons rebuild Cybertron. Unicron reanimates Megatron, possessing his body, planning to kill Cybertron, actually his brother Primus, using Dark Energon-infected Predacon corpses. Optimus and Wheeljack retrieve the AllSpark from deep space and return to aid their comrades. Optimus uses the AllSpark's container to extract and imprison Unicron's spark. Megatron, disillusioned with the prospect of tyranny, disbands the Decepticons and leaves Cybertron to start a new life. Optimus reveals he fused the Matrix of Leadership and the AllSpark into one and must fuse with Primus’ core to restore life to Cybertron. Bidding farewell to his comrades, Optimus Prime flies into Cybertron's core to begin a new era for the Transformers.