Although the use of the water resources in Uzbekistan is strongly limited by their quality, it has to be noted that there is a lack of information and data within the international scientific literature with regard to the water chemical characteristics of the Amu Darya River, one of the main water resources in Central Asia. To add to such knowledge, this paper examines the spatial and temporal variation of the water quality of the Amu Darya River in order to assess its degree of degradation and the main causal factors. The functional relationships of the pollutants with respect to the flow regime are investigated. Finally an "opportune temporal window" for water withdrawal for filling the reservoirs, in relation to human consumption, will be indicated. The high salinization levels of the waters are mainly due to the presence of sulphates and chlorine. At the up-stream site salinity, although presenting elevated concentrations, does not exceed palatability levels; after the 450 km point the opportune temporal window for water withdrawal with acceptable salinity values is reduced to the period from May to September. Two main driving forces govern the temporal variation of the salinity of the Amu Darya water: a low drainage density of the area which limits the salt loads induced by the natural runoff processes, and snow and glacier melting in the upper catchment area which promotes dilution of the dissolved salts during the high-flow period. During low-flow periods salinity is strongly influenced by the return of waters used for land washing and irrigation.