1869年，一列驶往美国德克萨斯州科尔比镇的列车，羁押着即将被送往当地处决的杀人魔头卡文迪什（威廉·菲德内尔 William Fichtner 饰），未料途中卡文迪什在同伙的协助下逃脱。同在囚犯车箱内的印第安人杀手Tonto（约翰尼·德普 Johnny Depp 饰）和联邦检查官约翰·雷德（艾米•汉莫 Armie Hammer 饰）历经万险，侥幸逃生，谁知却被后者投入监牢。约翰身为骑警的老哥丹（詹姆斯·戴尔 James Badge Dale 饰）率手下追捕卡文迪什，结果遭到对方残忍屠戮。随行的约翰在越狱逃走的Tonto的帮助下再度捡回一条命，并得知骑警中叛徒的真身。对于这个本应死掉的人来说，也许只有戴上面具才能匡扶正义。
白人和印第安人，两个原本没有任何交集的人踏上复仇之路……
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