Dark Samus is reborn, and takes control of the Space Pirates, using them as pawns for galactic conquest. Planning to spread Phazon across the universe, she starts creating Leviathans, giant meteorlike Phazon creatures that crash into planets and infect them with Phazon. In order to better understand Phazon, Dark Samus raids a Galactic Federation ship, the Valhalla, and steals its Aurora Unit (which is basically a good Mother Brain.)
The Galactic Federation, seeing the Space Pirates preparing for all-out war, hires Samus and a few other bounty hunters to help out. The new hunters are Rundas, who shoots ice, Ghor, who can connect with machines, and Gandrayda, who can shape-shift.
In the games opening level, Samus has to fight through a Pirate assault on a Federation ship, and makes her way to the planet Norion, where Dark Samus has just launched a Leviathan. samus than goes to reactivate the planetary defense system, planning to use satellite weapons to destroy the Leviathan before it crashes into the planet. During the level, she encounters Ridley in an LOTR-esque boss battle, and sucessfully destroys the Leviathan before it lands. Unfortunetly, Dark Samus arrives, and single-handedly defeats Samus and the other Hunters, corrupting them. As a result, Samus and the Hunters begin producing Phazon, and giving them the power to go into brief periods of 'Hypermode.'
After being fitted with a new suit to help her control the Phazon, Samus goes to other planets that have been struck by Leviathans (like Tallon 4 and Aether in previous games) Along the way, she is forced to kill the other Hunters, who have been completely corrupted by the Phazon. Furthermore, for every Leviathan destroyed, Samus absorbs its Phazon and becomes more corrupted, to the point where Samus' ship dosen't recognize Samus by the end of the game.
After destroying all the Leviathans (including one on the Space Pirate Homeworld, guarded by a Phazon-powered Ridley) Samus learns the source of Phazon: the Planet Phaaze, a sentient planet that hurls pieces of itself, which are Leviathans, at planets in an effort to conquer the universe. the Federation launches an attack on Phaaze, and a near fully-corrupted Samus has one last showdown with Dark Samus. Dark Samus eventually fuses with her stolen Aurora Unit, effectively recreating Mother Brain in all but name.
At last, Samus destroys the corrupted Aurora Unit, which starts a chain reaction that destroys the planet Phaaze and cures Samus of corruption. At the end of the 100% ending though, a dark looking ship with a striking resemblance to Samus' follows Samus thru space...the ship is presumably Dark Samus' ship.