In the scorching summer of 1519 in Spain, two clever swindlers, Miguel and Tulio, unexpectedly strike it rich after winning a rigged game of chance with the help of some fortunate dice from an unsuspecting opponent. They come into possession of a treasure map that allegedly leads to the legendary City of Gold, El Dorado. Unfortunately, their success is fleeting; they're soon uncovered and must flee from the authorities. In a desperate act of escape, they hide aboard a ship headed for the New World, which is commanded by conquistador Hernán Cortés.
While at sea, Miguel and Tulio's luck turns again as they find themselves captured and sentenced to slavery in Cuba. However, these resourceful con-artists are not ready to accept their fate. They escape their captors with the help of Altivo, a horse that belongs to Cortés, and seize a small boat to aid their flight.
As they journey through perilous waters, they start to recognize landmarks from the map, leading them to an enigmatic waterfall that marks the entrance to El Dorado. Tulio's skepticism contrasts with Miguel's hopeful enthusiasm, and their arrival at the falls brings an unexpected twist as they encounter Chel, a native woman under duress from pursuing guards. A curious depiction on a nearby totem featuring Miguel and Tulio riding Altivo prompts the guards to escort them and Chel through a secret entrance behind the waterfall, leading them straight into the fabled city.
Before the city's elders, including the benevolent Chief Tannabok and the sinister high priest Tzekel-Kan, Miguel and Tulio unwittingly fulfill a prophesy; an unforeseen volcanic eruption ceases the moment they start bickering. They are lavished with gold by Tannabok but horrified by Tzekel-Kan's intention to offer an innocent life as a sacrifice. Meanwhile, as Cortés and his forces land on new soil, they remain oblivious to the fierce competition brewing with the swindlers for dominion over this treasured land.
As the sun sets, Miguel and Tulio devise a plan with Tannabok to fabricate a vessel, pretending a divine will is propelling them to depart with their newfound wealth. Around this time, Miguel finds solace among El Dorado's inhabitants, while Tulio develops deeper feelings for Chel, leading to emotional turmoil. A celebration in their honor quickly descends into chaos when Tzekel-Kan demands the “gods” showcase their abilities against the city's top athletes. Despite their unpreparedness for the challenge, they strive to overcome it until Chel's clever intervention allows them to win by substituting the game ball with an armadillo. Touched by the experience of victory, Miguel spares the lives of defeated competitors, earning him respect from the citizens but drawing the ire of Tzekel-Kan, who realizes that real gods cannot bleed, thus eliminating the need for sacrifice.
As the city's populace rejoices in their newfound liberation, Miguel's thoughts drift toward the realm he has grown to cherish alongside its people, questioning his desire to leave. Overhearing Tulio's hopes to bring Chel back to Spain only exacerbates their conflict, hitting a boiling point during a grand fiesta. Tzekel-Kan, seizing upon the discord, conjures up a monstrous stone jaguar that wreaks havoc through the city. In the ensuing chaos, Miguel and Tulio manage to outsmart the creature, leading to the downfall of Tzekel-Kan and his jaguar into a mystical whirlpool said to connect to Xibalba, the realm of the dead.
In an uncanny turn of events, Tzekel-Kan resurfaces in the jungle, mistaken about Cortés and his men, believing they are true divine entities. He offers guidance to Cortés toward the hidden riches of El Dorado, setting the stage for turmoil as the two collide in their ambitions.
As Tulio and Chel decide to leave Miguel behind, an ominous cloud of smoke hints at Cortés' imminent approach. Realizing the threat he poses to their beloved city, Tulio suggests an audacious scheme: to ram their newly constructed vessel into the rock pillars beneath the waterfall, blocking entry into El Dorado. This drastic action risks their treasures and the fate of El Dorado’s warriors but is crucial for their collective safety. With citizens assisting in the endeavor, Tulio takes command of the boat, navigating it forcefully against the pillars. As the statue perched atop their vessel begins to teeter, Miguel and Altivo leap into action to aid Tulio in critical moments, solidifying their escape.
The blockade triggers a cave-in, resulting in the loss of their gold. Although initially disheartened by their vanished treasures upon Cortés’ arrival, Miguel, Tulio, and Chel realize they have achieved something greater: the preservation of El Dorado. With fresh determination, the trio sets off toward new adventures, leaving behind their cherished city.
