In the 22nd Century Lt. JT Marsh leads Able Squad, and elite unit of mecha pilots in the Terran military. Venus and Mars have both been terraformed and colonized, largely thanks to the help of Neosapiens, a genetically engineered slave race bred for hard labor. While Able Squadron and most of the Terran fleet are occupied with a pirate threat in the outer planets, charismatic Neosapien leader Phaeton launches a revolution. Neosapien forces quickly take control of Earth, Venus and Mars. Their previous uprising, fifty years earlier, was quickly put down by their human masters, thanks to the weaponization of Exo-Frame technology. Neosapiens were granted additional rights, including control of Mars, but they remained largely subjugated.
Realizing victory would require more than their own physical strength, Phaeton used his position as the Martian Governor to secretly build and stockpile weapons. He also manipulated the Exo-Fleet into travelling to the outer planets to confront the Pirate Clans. With the stage thus set, his revolt easily succeeds.
Learning of the revolution, the Exo-Fleet races back to the Homeworlds to mount a counter attack. The rest of the series follows a long and protracted war as the Exo-Fleet struggles to retake Earth and Venus with the help of local insurgents and Able Squad leading the charge.