After being set-up and betrayed by the man who hired him to assassinate a Texas Senator, an ex-Federale launches a brutal rampage of revenge against his former boss.

Machete and Sartana Rivera attempt to capture weapon dealers who have been supplying the Drug cartel. The military men are then all killed by the gangsters, who in turn are wiped out by another intervening party. Its leader murders Sartana while Machete is arrested by corrupt Sheriff Doakes and Deputy Clebourne. Doakes unsuccessfully tries to hang Machete but the President of the United States, Rathcock, intervenes. Machete is brought to the White House, where the president offers him US citizenship if he eliminates Marcos Mendez, a psychopath who is threatening to fire a nuclear missile at Washington, D.C. if the American government does not intervene to stop the rampant drug cartels in Mexico and the corruption of its government.