A Federale agent known only as Machete (Danny Trejo) is recovering from a painful past. A few years back, he was betrayed and set up by his former employer. What resulted from this betrayal was his wife and children being murdered by a drug lord named Torrez (Steven Seagal). Now, Machete has a chance to get back in the business, as he is hired by Booth (Jeff Fahey) to assassinate shady Senator McLaughlin (Robert De Niro), whose main stance is against immigration. At the last moment, Machete realizes this is yet another set-up, and he gets out just in the nick of time. Now, Machete is determined to get revenge once and for all against the people who are targeting him. With the reluctant help of his priest friend Padr (Cheech Martin), Machete is out to settle the score.