The story follows Eli Sisters (John C. Reilly) and Charlie Sisters (Joaquin Phoenix), two hitmen brothers in the pay of a wealthy man known only as The Commodore (Rutger Hauer), who tasks them with killing a man named Hermann Kermit Warm (Riz Ahmed). The Commodore claims that Warm stole from him and left town. Eli comments that he finds it suspicious how many people seem to steal from a dangerous man like the Commodore, but Charlie defends their employer. Warm is being tracked by John Morris (Jake Gyllenhaal), a scout also in the Commodore's employ. Morris finds Warm travelling by wagon train south to San Francisco, California with the Gold Rush and befriends him. Warm complains of the difficulties involved in his trip, and Morris helps him by buying him a horse and travelling with him to Jacksonville, where, unbeknownst to Warm, Morris has arranged to rendezvous with the Sisters brothers. When they arrive, Warm finds handcuffs in Morris' bags, realizes what his true intentions are, and threatens Morris with a gun. However, Morris overpowers him and restrains him. While he is tied up, Warm reveals that he is en route to California to find gold using a chemical substance of his own devising. The Sisters brothers have been sent to retrieve the formula from him, which he expects they will do by means of torture before killing him. Unable to stand the thought of allowing an innocent man to be murdered for the Commodore's profit, Morris frees Warm and leaves Jacksonville with him. On the road toward San Francisco, Warm reveals that his ultimate plan is to create a Utopian society, free from greed and other social ills, in Texas.