According to writer/director Robert Rodriguez, the idea to do a third movie in his El mariachi (1992) series came from his friend Quentin Tarantino who, knowing Rodriguez to be a fan of Sergio Leone, also suggested the title. Tarantino is given special thanks in the closing credits. - Actually Robert Rodriguez intended on making a trilogy from the get go. You can read that for fact in his book "Rebel Without A Crew".
After being introduced to High-Definition digital video by George Lucas in 2000, Robert Rodriguez made this film his personal test to push the limits of the cameras. They withstood all of the conditions, including the often intense Mexican heat, and allowed Rodriguez to experiment with various lenses, filters and frame speeds.
Almost the entire gunfight in the church was filmed with rubber guns, almost no squibs, and no physical damage to the church. Nearly all bullets, blood, explosions, and physical damage were added in post production.
There are several scenes that were leftover from El mariachi (1992) and Desperado (1995). The hotel escape was originally intended for Desperado, and the escape from the compound (while guarded in a jail cell) was included in the original script for El Mariachi.
The last movie Robert Rodriguez wrote as a member of the Writers' Guild of America. He left the WGA after completing the script saying that they "have too many rules and just take your money." He would later leave the Directors' Guild of America in early 2004, before the filming of Sin City (2005).
In the sidewalk café scene after Johnny Depp walks away, Rubén Blades pours the first drink of his wine on the ground. This is a symbolic gesture meaning "for those who have gone before" and is a salute to his murdered partner.
The real guns the filmmakers intended to use were delayed at the Mexican border for two weeks, so for the first two weeks of filming only rubber prop guns were used, with all the visual effects added digitally in post production. At first, Antonio Banderas was so thrown off by using silent prop guns that he was mouthing "bam" noises as he fired off fake shots.
There are a few references from the graphic novels of Sin City (2005), which Robert Rodriguez filmed after "Once Upon A Time In Mexico". First, when Sands shoots Ajedrez in the stomach after getting kissed by her, it's a identical picture from the graphic novel "A Dame To Kill For" that is number 2 in the Sin City maxi series. Earlier in the movie, when Barillo makes Sands blind, there is almost an exact picture from the Sin City book "Hell And Back". Other similarities are the scene with Mariachi and the priest in the confessional booth (as seen in the book "The Hard Goodbye") and the subplot involving facial reconstruction (as seen in "A Dame to Kill For").