The first people known to have occupied Central Asia were Iranian nomads who arrived from the northern grasslands of what is now Uzbekistan sometime in the first millennium B.C. At this time, cities such as Bukhoro (Bukhara) and Samarqand (Samarkand) began to appear as centers of government and culture. By the fifth century B.C., the Bactrian, Soghdian, and Tokharian states dominated the region. As China began to develop its silk trade with the West, Iranian cities took advantage of this commerce by becoming centers of trade.

Using an extensive network of cities and settlements in the province of Mawarannahr (a name given the region after the Islamic victories) in Uzbekistan and farther east in what is today China’s Xinjiang Uygur Autonomous Region, the Soghdian intermediaries became the wealthiest of these Iranian merchants. Because of this trade on what became known as the Silk Route, Bukhoro and Samarqand eventually became extremely wealthy cities, and at times Mawarannahr was one of the most influential and powerful Persian provinces of antiquity. The dominant religion until the 6th Century in the region was Zoroastrianism, but Buddhism, and Christianity also attracted large numbers of followers.

The wealth of Mawarannahr was a constant magnet for invasions from the northern steppes and from China. Numerous intraregional wars were fought between Soghdian states and the other states in Mawarannahr, and the Persians and the Chinese were in perpetual conflict over the region. Alexander the Great conquered the region in 328 B.C., bringing it briefly under the control of his Macedonian Empire.