During an operation gone wrong, federal police officer Machete loses his partner and is captured by a drug lord who kills his family and leaves him wounded. Machete survives and leaves Mexico for Texas where he is threatened by businessman Booth into assassinating Texas State Senator McLaughlin. Although Machete tries to refuse, Booth threatens to kill him unless he takes the job. The attempt is a set up and Machete takes the fall, shot by one of Booth's associates and framed for shooting the Governor in the leg. The stunt is meant to make illegal immigrants look bad and support McLaughlin's plan to deport thousands of them from the state.
Machete escapes Booth and goes to a hospital where he must escape again. Immigration agent Sartana Rivera is sent to find Machete but becomes attracted to him which makes her job more difficult. Luz, the leader of an immigrant aid movement called The Network, agrees to help Machete. Machete's priest brother Padre also joins their cause. To exact his revenge, Machete kidnaps Booth's family and finds evidence that Booth is involved with the same Mexican drug lord that killed his own family. Booth hires someone to try and kill Machete and has Machete's brother killed.
When Booth's fake assassination attempt on the governor goes public, an angry McLaughlin kills Booth and goes to the drug lord for help in murdering Machete. Machete rallies the Network and they head for Mexico, defeating border guards and confronting the drug lord. The drug lord kills himself and a nun, who turns out to be Booth's daughter, shoots McLaughlin as revenge for his killing her father. Although McLaughlin escapes with his injury he is killed by his own border guards who think he is an illegal Mexican trying to cross the border. Sartana finds Machete and offers him a green card then leaves with him to return to America.
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