This study examines the socio-economic and ethno-cultural development in the southern Aral Sea region from the 6th century BCE to the 9thcentury CE, focusing on settlements along the Amu Darya's right and left banks. Archaeological findings reveal that early urbanization was shaped by Achaemenid influence, followed by independent Khorezmian expansion. Hydrological changes, particularly shifts in the Amu Darya’s flow, significantly impacted settlement sustainability, leading to the decline of right-bank centers while leftbank hubs like Khiva and Khazarasp endured due to stable irrigation. The study highlights the interplay between environmental factors and human activity in shaping regional history.