The area of the park was inhabited 10,000 years ago by the hunter-gatherers of the Eldoradense culture. They were displaced around 1,000 CE by the Guaraní, who brought new agricultural technologies, and were displaced in turn by the Spanish and Portuguese conquistadores in the 16th century, though their legacy is still alive in this area (the name of the park and the river is Guaraní y guasu, "large water"). The first European to visit the zone was Álvar Núñez Cabeza de Vaca, in 1542; Jesuit missions followed in 1609.
The fauna of the park includes several endangered species: jaguar, jaguarundi, tapir, ocelot, tirica, anteater, pavas de monte, the jungle eagle, and the Yacare Caiman. One can also find birds like the vencejo de cascada and large toucans, mammals like the coatí, and a diversity of butterflies. The vinaceous-breasted parrot, named for its wine-colored plumage, is found in this park.
The Iguazú River ends in the Paraná River 23 km beyond the falls, after a 1320 km course. Inside the park it becomes up to 1,500 m wide and turns first south, then north, forming a large U-shape. Its banks are densely populated by trees, including the ceibo (Cockspur coral tree), whose flower is Argentina's national flower. The flora of the park also features lapacho negro and lapacho amarillo (family Bignoniaceae), as well as palmito trees and the 40-metre-high palo rosa (family Apocynaceae).