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- Voice artists in animated movies usually record their parts alone, with no other actors or actresses in the studio with them. In a break with this tradition, Kevin KlineKevin Kline and Sir Kenneth BranaghKenneth Branagh recorded their dialogue together similar to when Disney's Aladdin (1992) had Jonathan FreemanJonathan Freeman record many of his scenes with Gilbert GottfriedGilbert Gottfried.
- A series of sequels featuring Miguel, Tulio, Chel, Altivo, and even the armadillo going after other legends about gold was planned, similar to the [Shrek (2001)] film franchise, but following the disappointing box-office results, they were immediately cancelled.
- The armadillo that follows Miguel and Tulio throughout is named Bibo, after co-director Bibo BergeronBibo Bergeron.
- This is the first DreamWorks Animation movie not to earn a profit at the box office.
- The aesthetics of El Dorado and its inhabitants are a mixture of different pre-Hispanic cultures of Central America, in order to avoid connecting El Dorado to any particular geographical place. So, the buildings and temples are a composition of the Mixteco city of Mitla, in modern Oaxaca, Mexico, and the Mayan city of the Palenque. The features of the locals are distinctly Mayan, as well the murals and the Xibalba tradition. The weapons, attires, and human sacrifices customs are mostly of Aztec origin. Curiously, even though the inspiration comes from Central and Southern Mexico, the most widely accepted location for the real El Dorado legend was the Amazonian rain forest.
- This movie shares several attributes of its namesake, the ["Road" comedies] made famous by Bob HopeBob Hope and Bing CrosbyBing Crosby during the 1940s (which helps explain anachronisms, such as shared language, pop culture references, and lack of historical accuracy). In homage to the veteran comedians, during the song "It is Tough to be a God", Tulio and Miguel look into a rippling bowl of liquid. The reflection of Miguel briefly takes on the pronounced ears of Bing CrosbyBing Crosby, while the reflection of Tulio morphs into the distinctive profile of Bob HopeBob Hope.
- The story is inspired by Rudyard KiplingRudyard Kipling's "The Man Who Would Be King", featuring con men who try to trick the natives of an isolated city in Kafiristan, with disastrous results.
- The name of the Spanish General in the movie is Cortes, but in real life, the man who tried to find El Dorado was [?] Gonzalo Pizarro.
- In the Latin American Spanish version of the movie, Edward James OlmosEdward James Olmos also provides the voice of Chief Tanabok, Demián BichirDemián Bichir voices Tulio, Aleks Syntek, Miguel (they also sing "Qué Duro es ser Deidad" ("It's Tough to be a God")), while Manuel Mijares sings the rest of the songs.
- In the first scene that Miguel and Tulio enter the city the horse, Altivo, also mouths "El Dorado".
- Compared to everyone else in this animated film, Tzekel-Kan has his teeth individually carved out instead of a white line. This was intended to make him appear more life like, thus more intimidating.
- Denis LearyDenis Leary and Jim CarreyJim Carrey were considered the role of Miguel.
- Antonio BanderasAntonio Banderas and Adam SandlerAdam Sandler were considered the role of Tulio.
- [?] Jasmine Guy and Téa LeoniTéa Leoni were considered for the role of Chel.
- Martin SheenMartin Sheen and Christopher WalkenChristopher Walken were considered for the role of Chief.
- Kelsey GrammerKelsey Grammer and James GarnerJames Garner were considered for the role of Tzekel-Kan.
- Goran VisnjicGoran Visnjic and Kevin SpaceyKevin Spacey were considered the role of Hernán Cortés.
- In the unreleased sequel that was in production but cancelled, Tulio and Chel have a son as a result of their frequent ... encounters throughout the film.