身怀绝技的弯刀（丹尼·特乔 Danny Trejo 饰）在追查犯罪组织卡特尔的行动中，其女友兼搭档ICE特工莎塔娜（杰西卡·阿尔芭 Jessica Alba 饰）不慎遇害，弯刀也被作为杀人凶手判处绞刑。关键时刻，美国总统秘密将其招至华府，命弯刀前往美国和墨西哥的边界，调查革命武装组织头目马科斯·门德斯革命者（德米安·比齐尔 Demián Bichir 饰）是否有袭击美国的打算，一旦证据确凿即可将其抹杀。弯刀率先与圣·安东尼奥小姐（艾梅柏·希尔德 Amber Heard 饰）接洽，随后潜入墨西哥见到门德斯。此时的门德斯仿佛已经人格分裂，他将导弹的控制系统与自己的心脏相连，一旦遇害导弹便自动飞向美国华府，而他的人头又高达千万美金，以至于弯刀被迫担负起保护门德斯性命的任务。 　　返回美国的道路杀机四伏，凶险非常，更有意想不到的阴谋等待着他……During an operation of a Mexican Cartel, Machete Cortez and Sartana Rivera intercept the criminals alone, but another group arrives and a masked man kills Sartana. Machete is arrested, accused of killing his beloved Sartana and Sheriff Doakes hangs Machete. But the President of the USA Rathcock pardons and recruits Machete to kill the revolutionary Marcos Mendez that has threatened the USA with a missile with a bomb. Machete goes to San Antonio to meet the Miss San Antonio Blanca Vasquez that will be the liaison between Machete and President Rathcock. Then Machete goes to the brothel of Madame Desdemona to seek out the prostitute Cereza that is Mendez's mistress. Machete meets Mendez and learns that his heart is connected to the missile and only the arm dealer Luther Voz is capable to disarm the bomb. Now Machete needs to bring Mendez to the USA in less than twenty-four hours and save his new country in a dangerous journey with betrayals.