An ancient struggle between two Cybertronian races, the heroic Autobots and the evil Decepticons, comes to Earth, with a clue to the ultimate power held by a teenager.

Sam Witwicky leaves the Autobots behind for a normal life. But when his mind is filled with cryptic symbols, the Decepticons target him and he is dragged back into the Transformers' war.

Autobots Bumblebee, Ratchet, Ironhide, Mirage (aka Dino), Wheeljack (aka Que) and Sideswipe led by Optimus Prime, are back in action taking on the evil Decepticons, who are eager to avenge their recent defeat. The Autobots and Decepticons become involved in a perilous space race between the United States and Russia to reach a hidden Cybertronian spacecraft on the moon and learn its secrets, and once again Sam Witwicky has to go to the aid of his robot friends. The new villain Shockwave is on the scene while the Autobots and Decepticons continue to battle it out on Earth.

After the battle between the Autobots and Decepticons that leveled Chicago, humanity thinks that all alien robots are a threat. So Harold Attinger, a CIA agent, establishes a unit whose sole purpose is to hunt down all of them. But it turns out that they are aided by another alien robot who is searching for Optimus Prime. Cade Yeager, a "robotics expert", buys an old truck and upon examining it, he thinks it's a Transformer. When he powers it up, he discovers it's Optimus Prime. Later, men from the unit show up looking for Optimus. He helps Yeager and his daughter Tessa escape but are pursued by the hunter. They escape and Yeager learns from technology he took from the men that a technology magnate and defense contractor named Joshua Joyce is part of what's going on, so they go to find out what's going on.

A deadly threat from Earth's history reappears, and a hunt for a lost artifact takes place between Autobots and Decepticons, while Optimus Prime encounters his creator in space.