Optimus Prime is back and leads a team to Charr to retrieve the ship alloy from Galvatron. Galvatron guides them to it's location, but they confront a couple dangers and must fend off infected Transformers. Optimus and SkyLynx are the only ones not infected and barely get away with the alloy. The alloy is used to safeguard Optimus from the Hate Plague for his battle against Rodimus as the Matrix is the key to the cure.

On the run from Galvatron, Spike, Daniel and several Autobots enter a mausoleum and find a surprisingly not dead Optimus Prime. This would be cause for great excitement among Autobots. Unfortunately, however, Optimus is really under Quintesson control and is being used in a plan against his friends.

While testing a new ship alloy, Jessica Morgan and Gregory Swafford (who hates Transformers) stumbled upon the ship Optimus Prime was on and saved him. Some time afterward, Jessica gets hurt in a battle between Protectobots, Technobots and Terrorcons, causing her father and Gregory to plot revenge. They use Optimus to lure the Autobots into a trap, getting them infected with Hate Spores which make them go berserk. As the infection spreads, Sky Lynx seeks out a Quintesson that could bring Optimus back to life.

Galvatron learns what has been going on recently and meets up with the Quintessons. Rodimus again looks for answers, discovering the bitter history between Quintessons and Transformers. The Quintessons created the Transformers, but their creations rebelled against them. And the Quintessons are eager to exact revenge.

Starscream, in Scourge's body, attempts to complete three assignments for the damaged Unicron in exchange for getting a new body.

The evil Primacron plans to use an energy being named Tornadron to defeat the Transformers and help in his universal conquest. Meanwhile, the animal form Transformers leave during a battle between Autobots and Decepticons upon getting a strange signal. The signal was apparently sent by Primacron's own assistant, who believes this group of ""Primitives"" can defeat Primacron.

The Constructions use the newly created Trypticon to battle Metroplex, who is still unable to transform, on Earth. Sky Lynx tries to get the needed cog for Metroplex, which is with Blurr and Wheelie, but gets into a fight of his own. The Autobots and Decepticons continue fighting on Cybertron, until the Quintessons manage to immobilize them, leaving only Spike to save the day.

Octane is on the run from The Decepticons. He is forced to hide in a crypt, where the ghost of Starscream lies in wait and then takes over Cyclonus.

The Autobots make it out of Charr, but Rodimus is down and looks out. In reality, he has made a trip to the Matrix and learns the Quintessons are behind the kidnapping. After Rodimus is revived, a rescue mission is soon underway. Also, Scourge and Cyclonus finally track down a battle hungry Galvatron.

The destruction of Quintessa causes the Autobots to arrive at Goo and poor Springer loses some parts. Blurr and Wheelie are stuck in a hostile place and are in need of some help. Meanwhile, the Quintessons agree to give vital energy to the Decepticons so long as the Autobots are destroyed.

While everyone continues to rejoice in their victory, unknown assailants capture Ultra Magnus, Kup and Spike. After being told by a alien, a group of Autobots suspect the Decepticons are the culprits. But when they arrive at Charr, they find the Decepticons in no shape to pull off a kidnapping, meaning another is responsible.

The Quintessons trick the Decepticons into releasing the dangerous Trans-Organics. One of them, the Dweller, begins taking control over Autobots and Decepticons alike.

Metroplex's transformation cog is taken by Swindle and First Aid blames himself for not stopping him. Meanwhile, Galvatron threatens to use a powerful weapon.

Being the leader takes it toll on Rodimus and his attempt to relax gets him into a fight, in which he loses the Matrix. The Stunticons escape with it and Rodimus reverts to Hod Rod. At first, Hod Rod is perfectly fine with no longer being in charge, but he soon understands he must get the Matrix back. It will not be easy, though, as Scourge has already seized the power of the Matrix.

Grimlock becomes a genius after trying to stop anti-electrons (released by Scukzoid and Slizardo) from causing disruptions in the new power generator. This proves very useful to the Autobots, especially when Grimlock learns Unicron is the source of the anti-electrons. The Autobots journey to Unicron to prevent more anti-electrons from being obtained, but Galvatron and his forces are also heading that way.

Galvatron goes into therapy, but it does not exactly agree with him. Every one of the doctors' attempts at treating him fail before they consider using one last option. Cyclonus tries to stop them, however, after learning it would make the Decepticon leader an invalid.

After the Autobots interfere with one of his plans, Victor Drath gets help from Ol' Snake (none other than the notorious Cobra Commander) to create artificial human bodies. Rodimus, Springer, Ultra Magnus and Arcee get caught and placed in the artificial bodies. Seemingly human, they will have to find a way to reverse what was done to them and stop Drath from using their original bodies against Autobot City.

The Quintessons use Wreck-Gar, Cyclonus, Ultra Magnus and Marissa as research subjects, watching how they interact. Unfortunately for all of them, the ship they are on is heading for a black hole and this unusual group will have to work together to survive.

An alien is discovered to have a powerful weapon that fires crystals, which are taken from a creature Kup knows of, Chaos. Galvatron plans to construct his own powerful weapon on Chaos' home and several Autobots race to prevent him from using it on Cybertron.

The Quintessons plan to use a portal through time to prevent the Transformers' revolt against them. Several Autobots wind up getting sent back to the fight and a robot with an important future arrives in the present. And the Quintesson time portal begins to have disastrous effects on the universe.

The Decepticons attack a planet home to several Autobots and easily win as these Autobots prefer peace to fighting. Once the Autobots arrive, they try to persuade their peaceful comrades that only battling the Decepticons will solve their problems.

Daniel leaves a banquet being hosted by his parents. He and Grimlock end up discovering a Quintesson chamber and get stuck in a magical world.

The Junkions fall victim to subliminal messages from the Quintessons, who are trying to get a journal off the Planet of Junk. This also causes the Junkions to attack Sky Lynx and Astrotrain, which brings the Autobots and Decepticons into the situation. Unfortunately, a screw up makes the Junkions send out the subliminal messages on their own, bringing about mass confusion and destruction.

Two planets are locked in a destructive war and the Autobots attempt to bring about peace. Things do not go so well, however, until a Quintesson Journal is found and provides evidence of Quintesson involvement in the war.

Octane locates the defeated Trypticon and brings him to Carbombya. There, they follow orders from Fakhaddi in order to get energon. They begin stealing landmarks around the world for him.