Fall of Cybertron takes place after the events of it's predecessor in which the Autobots and the Decepticons are still at war with each other. After defeating Trypticon, the Autobots have slowed down the attacks of Megatron and his minions of Decepticons however they now have a new problem.

Cybertron is dying and the Autobots, led by Optimus Prime, are unable to save it and must do what they can to survive by leaving their home and find a new world to live on. In secret they have built a massive ship called The Ark and are now readying it for flight. Unknown to Optimus is that the Decepticons are aware of their plans and are planning their own escape as well and will try to stop them at every chance they get as both factions fight to survive.

The game play, like War for Cybertron, is a third-person shooter where the player can use their Transformer to transverse through the level and use their ability to transform into vehicles to advance through the stage when they see fit. Throughout the game the player can use Energon they pick up from fallen enemies and can use them at kiosks being ran by Teletran 1 and buy weapons and upgrades. The health system now features something similar to Halo with regenerating shields and each Transformer the player uses has special abilities, such as the ability to be invisible (i.e. Jazz), the player can use to help advance in the level.

Unlike War for Cybertron where the player can choose which side to play, Fall of Cybertron has a single campaign with chapters that tells the story through either the Autobots or Decepticons and at times intersect their encounters. Some of the characters the player can control include Optimus Prime, Megatron, Starscream and even Grimlock to name a few. There is also multiplayer with the standard Deathmatch and Team Deathmatch modes along with Conquest and Capture the Flag with class-based characters the player can customize by earning experience points. There is also a "Horde mode" called Escalation where up to four players face waves of increasingly difficult enemies.