In 1862, in the American Southwest during the Civil War, three bounty-hunters ambush Mexican bandit Tuco Ramirez, who shoots them all and escapes.
Elsewhere, mercenary "Angel Eyes" interrogates former Confederate soldier Stevens for the alias of Jackson, a soldier who stole a cache of Confederate gold. Stevens gives the name "Bill Carson", offers Angel Eyes a bribe and then draws his pistol. Angel Eyes kills him and, intrigued about the gold, kills his own employer.
Tuco is rescued from more bounty-hunters by an unnamed drifter, whom he nicknames "Blondie". Blondie delivers Tuco to a sheriff and collects his $2,000 bounty. As Tuco is about to be hanged, Blondie severs the noose by shooting it and sets him free. The two escape and split the bounty. They repeat the process in other towns until Blondie grows weary of Tuco's complaints and strands him in the desert.
Bent on revenge, and after one failed attempt with his gang, Tuco catches up with Blondie and force-marches him across the desert until he collapses from dehydration. A runaway ambulance arrives with several dead Confederate soldiers and a near-death Bill Carson, who asks Tuco for help, offering $200,000 in gold, buried in a grave in Sad Hill Cemetery. When Tuco returns with water, Carson has died. However, before dying, he revealed the name on the grave to Blondie. The two reluctantly set aside their grudge and work together, since Tuco only knows the name of the cemetery while Blondie knows which grave to dig.
Posing as a Confederate soldier, Tuco takes Blondie to a nearby mission to recover. There, Tuco reunites with his brother, Pablo, who left his family to become a priest when Tuco was a child. Their meeting does not go well and Tuco angrily leaves with Blondie.
On the way, Tuco yells pro-Confederate statements to an approaching group of soldiers who turn out to be a Union patrol. The two are taken to a prison camp that Angel Eyes has infiltrated as a Union sergeant in his search for Bill Carson. Having posed as Carson, Tuco is taken away for questioning. Under torture, he reveals the name of the cemetery and is sent away to be hanged. Knowing Blondie would not reveal the name on the grave, Angel Eyes recruits him into his search. Tuco escapes hanging by killing a henchman working for Angel Eyes, then goes to an evacuated town where Blondie, Angel Eyes and his gang have arrived.
Blondie finds Tuco and together they kill the gang, but Angel Eyes escapes. En route to the cemetery with the gold, the duo find themselves in a skirmish between the Union and the Confederacy over a strategic bridge. Blondie decides to destroy the bridge to disperse the armies and clear their path. As they wire the bridge with explosives, Tuco suggests they share the location of the grave in case either is killed. Tuco reveals the name of the cemetery is "Sad Hill" while Blondie says "Arch Stanton" is the name on the grave.
After the bridge is demolished, Tuco steals a horse and rides to Sad Hill to claim the gold for himself. Blondie catches up to him as he digs up the grave, but both are surprised by Angel Eyes as Tuco finishes digging up the grave. When it is revealed the grave contains no gold, Blondie admits lying about the name. He then places a rock in the middle of the cemetery's pavement on which he says the true name is written. The other two men understand they must kill or be killed to find out the name on the stone and step slowly away from each other.
The iconic Mexican stand-off, with Tuco seen on the left, Angel Eyes in the middle, and Blondie on the right. The scene is accompanied by Ennio Morricone's "The Trio".The men stand around the pavement in a Mexican stand-off waiting for one of them to draw his pistol. Angel Eyes draws first and Blondie kills him. Tuco discovers his gun is unloaded. Blondie reveals that he had previously unloaded Tuco's pistol, and the gold is in the grave marked "Unknown" beside Stanton's.
Tuco digs up the grave and is elated to find large bags of gold. However, Blondie orders him at gunpoint into a hangman's noose beneath a tree. With his hands bound, Tuco is forced to stand atop an unsteady grave marker while Blondie takes his half of the gold and rides away. As Tuco screams for mercy, Blondie severs the rope with a rifle shot, dropping Tuco face-first onto the gold. Tuco furiously curses Blondie, who disappears over the horizon.
