Quivira is situated in a valley in an area known as La Selva de las Serpientes ('The Serpent Jungle'). In the centre of the valley is the above-ground portion of the city, which includes a vast temple complex with the Pyramid of Omatihicoya at the centre. The surrounding architecture includes aqueducts, temples, plazas and numerous other buildings, many decorated with the image of a serpent.
From the top of the Pyramid of Omatihicoya can be seen the Temple of the Serpents, perched on a ridge overlooking the valley. This Temple contains the only known access point to the underground portion of the city, referred to by Marisa Chase as a representation of Mitzican (the Quiviran underworld). The caves descend deep into the mountain through vast caverns filled with carved monoliths and ancient wooden walkways before reaching a sealed stone door - the Doorway of the Gods. The door can only be opened using the Amulet of Eternity as a key, and grants access to the lower caverns.
The lower caverns have been sealed for centuries, and contain the last surviving tortured corpses of the Quivirans. The way forward is immediately barred by the Lake of Ghosts, said to be formed from the tears of the goddess Chihopotex. Built into the walls of the lake is the rest of the city. On the other side of the lake is another door which allows entry to the sacred enclosure surrounding the Golden Abyss, with the Throne of Gold at its centre.
The first known discovery of Quivira since it was abandoned was by Friar Marcos de Niza, an agent of the Sete Cidades in search of the Seven Cities of Gold, and his expedition including his guide, Esteban, and a party of Spanish Conquistadors. Upon discovering the Temple of the Serpents bore a sign of seven, Marcos assumed he had discovered one of the Seven Cities (it was in fact a representation of the seven gods in Quivira's Circle of Heaven) and entered the city, reaching the Throne of Gold itself. Seeing the suffering of the people, Marcos feared the city was a place of evil, and sacrificed Esteban at the Throne to appease the devil and seal the gates of hell. When he left, he took the Amulet of Eternity with him to seal the Doorway of the Gods. The Conquistadors, however, cared only for the gold they had seen at the Golden Abyss, so to prevent them revealing what they had found Marcos had them murdered, and left the Amulet at their grave site where it would eventually be found by Vincent Perez. Marcos was later forced to lead an expedition to Quivira, but to hide its location he travelled north into the southern United States, forever branding himself a liar and leading to modern theories that Quivira is located in the southern USA.
Vincent Perez became obsessed with solving the mystery of the dead Conquistadors, and tried to follow Marcos' trail back to Quivira, but ultimately succumbed to terminal cancer before he could do so. His granddaughter, Marisa Chase, was aided by Nathan Drake in following Perez's trail, and then picking up Marcos', back to Quivira. They raced against Panamanian revolutionary Roberto Guerro and rival treasure hunter Jason Dante, reaching the Throne of Gold first and discovering what Marcos had done. They also discovered that the gold was all radioactive due to uranium deposits buried under the mountain, and the mutations caused by it was what had wiped out the Quivirans. Nate determined not to allow the gold to leave Quivira, and Chase detonated explosives placed by Guerro to destroy the cavern. Both Jason Dante and Guerro were killed in the collapse of Quivira, while Nate and Chase escaped with the aid of Victor Sullivan.