The increasing global air temperature will trigger changes in the global mean water vapor, precipitation patterns and evapotranspiration, which further leads to changes, for instance, instream flow, groundwater flow and soil moisture. Projections of future changes in thehydrological regime of the Aral Sea Drainage Basin (ASDB) in Central Asia are however highlyuncertain, due to complexities of natural and engineered water systems of the basin. The AmuDarya River Delta (ADRD) is vital to the water budget of the Large Aral Sea, the livelihood inUzbekistan and Turkmenistan, as well as the surrounding riparian ecosystem. This study attemptsto investigate responses of river flow in the Aral Sea Drainage Basin and key riparian vegetationspecies (of the so-called Tugai community) in the Amu Darya River Delta to projected futureclimate change. Results from hydrological model and outputs from multi-GCM predictions providea basis for conducting more robust quantitative analysis of possible future hydro-climatic changesin the Amu Darya River Basin. A qualitative synthesis of the suitability of Tugai is furthermoreperformed in order to increase the knowledge of the riparian vegetation status under thechanging hydro-climatic conditions. The results show that the averaged temperature in the ASDBis likely to continuously increase and yield a total increase of about 2 °C ~ 5°C by 2100. Thechange trend of the annual regional precipitation of 2100 is relatively unclear, with estimatesranging from 50 mm lower than today to 75 mm higher than today. Modeled ensemble means (EM)river flow, obtained from hydrological modeling of climate output from multi-GCM projections,converge on showing future decreases in river runoff (R). Projected absolute R may decrease tozero around 2100, implying no surface flow and a dry out near the river outlet. The relationship ofwater flux between upstream and downstream will be changed dramatically due to climatechange. More specifically, R of the upstream region will decrease, and it is likely to becomeinsufficient for feeding downstream river reaches as it used to. The decreased river flow in thedelta may accelerate the desertification and salinization processes. Consequently, speciestransitions may occur, along with degradations of the existing Tugai communities. Theuncertainties of hydro-climatic change projections to some extent hinder the understanding of thedynamic hydrological-climatic-ecological system. However, the detailed responses of the delta toclimate change based on multiple qualitative and quantitative analyses provide an important basisfor the formulation of more robust forecasts on the future ecological development in the ADRD, and further for recommendations of measures to mitigate the ecosystem’s deterioration under achanging climate.