Evidence of human activity in the Qosqo (Qusqu, Cusco, Cuzco) region dates as far back as the 6th century BCE, but it was not until four thousand years later in 1000 BCE that a permanent settlement began in the city's modern urban center. This nearly three thousand years of inhabitance makes Qosqo among the oldest continuously inhabited cities in the entire Americas, north or south. The tribes which resided here during those early periods have been labeled the Markavalli or the Chanapata, with later groups arising known as the Alcavisas, the Wallas, and the Sawasirasthe.

Conquest by the Huari (Wari) empire began in 750 CE and resulted in the first imperial domination of the region. Under these northern occupiers, the Incans, known as the Quechuans for their Quechua language, acquired new knowledge of terrace-building techniques and were included into the vast Huari road system. Such roads would later be expanded by the Incans such that Incan roads were similar in both extent and importance to those in ancient Rome. The original settlement at Qosqo remained inhabited while the Huari establihed their own city nearby, named Pikillaqta. Of equal importance were advances in construction technology through the application of Huari methods. The Incans acquired the skills which would enable to build the stunning and mammoth structures which remain to this day. Yet it was the decline of the Huari, at or before 1200, which permitted Qosqo the freedom to expand into the region's dominant city-state.

The emergence of Qosqo's power following the the Huari disintegration was a result of the Quechuans' success at forging strong economic, political, and cultural bonds with the populace in neighboring territories. Such centralization of influence enabled the city-state to acquire a regional kingdom, governed by the Sapa Inca, the Quechuan ruler. From this title derived the term by which the Quechua would become best known, the Incans.

An assault by the neighboring Chanca tribe prompted the emergence of the conquering ninth Sapa Inca, Pachacuti. Raising an army and steathly expanding Incan alliances, Pachacuti led the kingdom to victory over the Chanca, and thereafter undertook a series of ambitious campaigns to spread the Incan boundaries.

Under this enlightened ruler Tawantinsuyu, the Incan empire, was created. It was divided into four provinces (suyus) which are today recognized as encompassing, respectively, the northern, the eastern, the southern and the western portions of the empire beyond Qosqo. From these provinces came the imperial name of Tawantinsuyu: the land of the four regions. The Incans invested heavily in constructing numerous roads to traverse and connect this new and vast domain. Each road ultimately led to Qosqo, which the Incans began to call "the navel of the world."

Spiritually, the Incans considered Qosqo to be the center of all human existence. In Quechua, Qosqo is equivalent to the "vital center" or the "origin of energy". Those who lived in the city believed they lived upon sacred ground, the result a legend that Qosqo had been settled by the descendants of the Incan dieties. Enclosing both the city and the surrounding valley are twelve "guardian" mountains representing the apos (apus), or "earthly divine spirits", who protected the living beings below. Thus Qosqo was a pilgrimage destination commanding great reverence as the Incan sought to experience the enegry which was attributed to the capital city.