The "Man with No Name" concept was invented by the American distributor United Artists, looking for a strong angle to sell the films as a trilogy.

The first film has the Man with No Name arriving in the Mexico–United States border town of San Miguel, the base of two rival smuggling families, the Rojos and the Baxters.

The Man with No Name, referred to by the old undertaker Piripero as "Joe", plays them against each other by collecting prizes for giving information, capturing prisoners and killing men, while also helping a woman, her husband and their son, held captive by the ruthless Ramón Rojo, to escape.

After the last remaining Rojo brother, Esteban, is killed by Silvanito while trying to shoot from a window, the Man with No Name departs from the now-peaceful town.

Both searching for the psychopathic Mexican bandit known as "El Indio" who escaped from jail, they rival each other, but realize that to kill him, they must work together.

El Indio transfers his gang to Agua Caliente, Mexico, where Manco and Mortimer attempt to steal the money to take it back to the Bank.

El Indio discovers their plot but lets them escape as part of an operation to murder all but one of his associates, to split the money in two instead of with the entire gang.

Manco piles the bandit corpses in a horse-drawn cart and rides away with the stolen bank money to collect his bounty earnings.

During their journey to the treasure, they are arrested by Union Army soldiers and taken to a prison camp where Angel Eyes is posing as a Sergeant.

Blondie takes up a burnt-ended cigar and a rock and tells the others that he will write the name of the grave marker on the bottom of a stone.

A Fistful of Dollars is an unofficial remake of Akira Kurosawa's 1961 film Yojimbo starring Toshiro Mifune, which resulted in a successful lawsuit by Toho.

Four actors appear twice in the trilogy, playing different characters: Lee Van Cleef, Gian Maria Volonté, Luigi Pistilli, and Joseph Egger.

Composer Ennio Morricone provided the original music score for all three films, although in A Fistful of Dollars he was credited either as "Dan Savio" or "Leo Nichols", depending on the print.