Machete (Danny Trejo) is a skilled criminal who is investigating the criminal organization Cartel. His girlfriend and partner, ICE agent Shatana (Jessica Alba), is accidentally killed, and Machete is also sentenced to death by hanging as a murderer. At a critical moment, the US President secretly recruited him to Washington, D.C., and ordered Machete to go to the border between the United States and Mexico to investigate whether the leader of the revolutionary armed organization, Marcos Mendes (Demián Bichir), intends to attack the United States. Once the evidence is conclusive, he can be eliminated. Machete first contacted Miss San Antonio (Amber Heard), and then sneaked into Mexico to meet Mendes. At this time, Mendes seemed to have split personality. He connected the control system of the missile to his heart. Once killed, the missile would automatically fly to Washington, D.C., and his head was worth tens of millions of dollars, so Machete was forced to take on the task of protecting Mendes' life. The road back to the United States is full of dangers and dangers, and there are unexpected conspiracies waiting for him...