The Silk Road trade network was arguably the most important network of global exchange and interaction prior to the fifteenth century. On the question of how and when it developed, scholars have focused mainly on the role of either the empires dominating the two ends of the trade network or the nomadic empires on the Eurasian steppe. The sedentary people of Central Asia have, however, mostly been neglected. This article traces the development of the city-states of the Tarim Basin in eastern Central Asia, from c. 2000 bce to 400 bce. It argues that the development of the city-states of the Tarim Basin is closely linked to the rise of the ancient Silk Road and that the interaction between the Tarim polities, the nomads of the Eurasian steppe and the Han Empire was the central dynamic in the creation of the ancient Silk Road network in eastern Central Asia.