Lucas Cano, (Machete) an ex-bodyguard for the Mexican President, tired of his life style, retires to a remote small town in Mexico, in hope of finding peace. But things do not work out for him the way he wants them to. First, he must confront several drug dealers who smuggle illegal immigrants into the United States, forcing them to smuggle drugs. Then, Machete finds out that his old Vietnam friend, who now works for the CIA in Arizona, has been assigned to arrest Machete, and take him back to the US for some old charges. Machete's health is deteriorating rapidly. He is constantly bleeding internally, but he won't stop drinking and smoking. Panchito is a little boy Machete met in a street fight, and the little boy, claiming not to have any family, decides to hang out with Machete and tries to help him change his life style. Machete does not know that a higher power is watching out for him.