Paleo-climatic, environmental, archaeological studies and historical accounts concerning the behavior of the Aral Sea during the last 2000 years point to a number of water level regressions similar or deeper than the modern one. This article is focused on the causes of such regressions, which are variously attributed to climatic change, diversion of river courses and anthropogenic water withdrawal. The first factor has been researched by several geo-specialists and its potential impact has been preliminarily evaluated. The second factor has been considered only in the case of the Amu Darya river. The third factor-water withdrawal for irrigation purposes-has been hypothesized, though never deserved specific analysis. The article provides a quantitative evaluation of the total hectares covered by the medieval urban systems of the Syr Darya and Amu Darya river basins, and of the coefficient of water use per hectare of walled towns during the X-XII centuries AD. Estimates of annual volumes of anthropogenic water withdrawal allow the investigation of the complex interaction of the three factors above in determining the hydrological conditions of the Aral Sea. On the basis of the calculation of possible scenarios of water mass balance, the occurrence of transmission losses by medieval diversions of the Syr Darya course has been suspected as the main cause of lake regressions, which is supported by geological considerations, archaeological data and historical accounts.