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The game starts out with Sideswipe contacting Optimus to notify he is starting search and rescue after Trypticon's blasting of Iacon. He recieves a transmission from Ratchet concerning wounded Autobots, after which he finds Ratchet apparently offline. After Sideswipe moves some debris, Ratchet comes back online and comments,"Megatron fights dirty." They then head to a safer location and pass on to Optimus the location of the Decepticon Datacore holding information on Trypticon. Ironhide and Bumblebee volunteer for the mission. The two blast their way through the datacore's defenses and hack it. Unfortunately, as they try to escape, Megatron shows up and blasts them with his fusion cannon, stating,"I shall not suffer thieves!" Air Raid later bombs the Kaon prison that Ironhide is being held in, temporarily disabling the prison's defenses. He proceeds to rescue Bumblebee from interrogation with Air Raid providing backup, and escapes back to Iacon. Armed with the information Ironhide and Bumblebee retrieved, Air Raid heads to The Core and cuts off Trypticon's Dark Energon supply after dealing with some Core Mites and Corrupted Worms. Afterwards, Optimus and Bumblebee mobilize in order to protect a supply convoy. Bumblebee has plenty of fun "cleaning thing up", saving Optimus's housing, and blowing up some Decepticon AA guns. Air Raid and Jetfire then get to work protecting supply ships, providing backup, and defusing bombs set by Skywarp and Thundercracker, and down a decepticon cruiser. Air Raid ends up fighting with Thundercracker after listening to an endless stream of insults, and damages him so bad his systems start shutting down and says,"My Afterburners! Systems shutting down. I've got to get out of here." Jetfire shows up again, chasing Skywarp. Air Raid then chases the pair of decepticons out of Iacon state. The Aerialbots then head to the Orbital Debris and take out the Dark Energon relays powering Trypticon's defenses. Optimus, Bumblebee, and Ironhide gather all the Autobots and manage to defeat Trypticon, knocking him off the platform he was standing on.
Megatron surveys the damage Trypticon's single blast has caused to Iacon, and comments to Skywarp and Starscream,"I knew our weapon would be formidable, but this... this is astonishing!" He then tells them to "clean up the area". This confuses Starscream, so Megatron punishes him by reasigning him to guard duty, a task that Starscream believes is grunt work. Megatron then hunts down Ratchet, and kicks him off a cliff in slow-mo. Meanwhile, Starscream and Thundercracker take out their frustrations on a group of Autobots they find. Megatron gets mad at Starscream again, because he abandoned his post, leaving a sleeping Trypticon unprotected. This frustrates Starscream, and he goes off blasting more Autobots. Next, Soundwave and Barricade contact Megatron and notify him of Autobot intruders in a Kaon datacore. They eliminate the intruders, and meet up with Megatron just as he shoots Bumblebee and Ironhide into submission. They manage to extract information from Bumblebee on Autobot supplies and strongholds. Skywarp and Thundercracker are then sent to eliminate key Autobot facilities,including a communications unit and an Energon Relay. Meanwhile, Starscream is ordered to turn the Dark Energon supply at the Core back on. He does, but forgot to focus the beam, and Megatron punishes this by puting him on the leading edge of the Iacon raid. Megatron then orders all able troops to attack Iacon city at once. Barricade is ordered to weaken buildings so air strikes can take them out. He also gets into a fight with Sideswipe, but Starscream orders him to attack the Council Chambers just as he's about to take Sideswipe offline. After fighting through a horde of enemies and getting inside, Barricade comments on finding the chambers empty,"I'm no great military strategist, but this seems like an awful lot of work for an empty room." Megatron the contacts Starscream and tells him that from Trypticon, he saw the council members leave hours ago. Thundercracker is dispatched to plant a beacon on the council members ship. He succeeds, but Jetfire and Air Raid had already taken out Trypticon's power supply and cannot finsh blasting them out of the sky. Megatron orders him to defend Trypticon, along with all the other Decepticons attacking Iacon. Megatron is inside Trypticon, "engaging in some damage control". He destroys some Autobot's attacking Trypticon's power chamber, but it's too late. Megatron races to Trypticon's head and retrieves his data cortex in order to keep it out of Autobot hands. He breaks through Trypticon's eye and returns to Kaon. Soundwave greets him and Megatron gives him a brief speech, ending with,"The Autobots may have one the day, but I still have the upper hand."
The Autobot and Decepticon campaigns happen simultaneously, unlike in War for Cybertron, were the Decepticon missions come first chronologically, then the Autobot missions come last.