In the 16th century, Don Aguirre leads Spanish conquistadors to South America in search of the Tears of the Moon, a mythical tree whose petals can cure any illness, heal any injury, and lift any curse. After most of his men died in the jungle, the survivors are nursed back to health by a local tribe using the tree petals.
When the village chief refuse to reveal the location of the tree, Aguirre stabs him and his men started attacking the villagers and destroy their village. As punishment, the conquistadors became cursed by the dying chief to never be able to leave sight of the river or the jungle would take them back to it for all eternity.