The film tells the story of three men who pursue, often at the expense of others, information about the location of a buried treasure of coins. The first character introduced in the movie is Tuco Benedicto Pacifico Juan Maria Ramirez - called Tuco - , who has a bounty on his head for numerous crimes. Tuco has a partnership with Blondie in which the latter turns him in for the reward money which the two then split after Blondie saves Tuco from hanging at the last moment. Meanwhile, a third character called Angel Eyes has learned of a hidden trunk of gold owned by a Confederate soldier named Bill Carson. He sets off to find the gold.
Soon, Blondie grows tired of his relationship with Tuco, and leaves Tuco in the desert with no water. Tuco survives and is intent on exacting revenge on his former partner. He finds Blondie, and turns the tables by planning to abandon him in the desert. However, before Tuco can complete his torture in the New Mexico desert, a runaway stagecoach full of dead and dying Confederate soldiers appears. Bill Carson, the man with knowledge of the whereabouts of the gold, dying from thirst, persuades Tuco to get him a drink by disclosing the name of the graveyard where the loot is located. As Tuco goes for the water, Carson dies, but not before revealing the name on the grave to Blondie.
Dressed in the uniforms of the dead soldiers, Tuco takes Blondie, near death, to a local Catholic mission run by his brother, a priest. While Blondie recovers, Tuco and his brother confront each other about the mistakes each has made in life. After leaving the mission, the two, still impersonating Confederate soldiers are captured and taken to a Union prison camp. Angel Eyes has followed the trail of Bill Carson to the prison camp and is posing as a Union Sergeant.