Uplistsikhe is identified by archaeologists as one of the oldest urban settlements in Georgia. Strategically located in the heart of ancient kingdom of Kartli (or Iberia as it was known to the Classical authors), it emerged as a major political and religious center of the country. The town’s age and importance led medieval Georgian written tradition to ascribe its foundation to the mythical Uplos, son of Mtskhetos, and grandson of Kartlos.
With the Christianization of Kartli early in the 4th century, Uplistsikhe seems to have declined in its importance and lost its position to the new centers of Christian culture – Mtskheta and, later Tbilisi. However, Uplistsikhe reemerged as a principal Georgian stronghold during the Muslim conquest of Tbilisi in the 8th and 9th century. The Mongol raids in the 14th century marked the ultimate eclipse of the town; it was virtually abandoned, and only occasionally used as a temporary shelter in times of foreign intrusions.