Ezio: "You are... gods." Minerva: "No. Not gods. We simply came... before." ―Ezio Auditore da Firenze and Minerva, on the nature of the Isu, 1499.[src] Trio 1 Three representatives of the Isu: Juno, Minerva and Jupiter The Isu,[1][2] known to humanity as the First Civilization,[3][4] Those Who Came Before,[5] or the Precursors,[6] and classified as Homo sapiens divinus by Abstergo Industries,[7] are an ancient and advanced species of humanoids that were perhaps the first known to call Earth their home.

Unlike most other species on Earth, the Isu possessed a triple-helix DNA structure[7] along with six senses rather than five.[8] They were an inhumanly intelligent, extremely long-lived and advanced species, being responsible for the creation of the Pieces of Eden, as well as the human race itself and many other species of the Homo genus, whom they used as a domestic workforce. They genetically altered several Homo species with the Pieces of Eden to make them anatomically similar to the Isu, the only differences being the height and the size of the skull.[2] With early humans unable to comprehend the Isu for what they truly were, they came to be revered as deities.

Following a rebellion led by the Human-Isu hybrid Eve, a war broke out between the Isu and their human slaves. This decade long war, coupled with the onset of what would be referred to as the "Toba catastrophe", would see the Isu gradually decline, and ultimately fall extinct. Despite this, their legacy would live on for thousands of years in various myths and legends, becoming the basis of many human religious ideals. Some of their Pieces of Eden managed to survive the catastrophe, and became a pivotal desire for both the Knights Templar and the Assassin Brotherhood, who waged a war of their own for the Pieces.