Ex-Federal Agent Machete mourns his beloved Sartana, who was murdered in the drug war, when the President of the United States sends him on a true ascension mission: Machete is supposed to eliminate the crazy Mexican cartel boss Mendez, who threatens the US capital with a nuclear missile. The detonator is connected to Mendez's heart, and only one man can defuse the bomb: mastermind Luther Voz, a very rich and eccentric arms dealer with fantasies of omnipotence. Chased across Mexico by numerous pursuers and repeatedly confronted with hot ladies and their very special weapons, Machete have a full 24 hours to stop global anarchy ...