A hardened ex-Federale named Machete is recruited by the President of the United States for a mission that would be impossible for just any mortal man. He must take down a madman revolutionary and an eccentric billionaire arms dealer who have hatched a plan to spread war and anarchy across the planet. The mission sends him into battle with a host of opponents, all while battling his way through Mexico and heading toward his ultimate target.

As Machete sets out on his mission, he encounters a network of allies and foes. A mysterious beauty crosses his path with her own agenda while he dodges assassination attempts and sabotage from all corners. His quest brings him into the orbit of a weapons expert who seeks to wreak havoc on an international scale with a new deadly weapon. Brimming with betrayal, the plot weaves a high-octane tale of vengeance, justice, and espionage beneath the fiery skies of a dying world.