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Identifying the links among ecosystem services (ES) supply, social demand and human well-being is important to realize sustainability, especially in mountain-oasis-desert (MOD) areas, which are facing an intense conflict between socioeconomic development and ecological conservation. Using a biophysical model, we mapped six ES in the Manas River Basin, which is a typical MOD area. A questionnaire survey was employed to evaluate social demand for ES and human well-being in four different regional units (i.e., high mountain, low hills, oasis and desert) in our site. Spider diagrams were applied to identify the links among ES supply, social demand and human well-being. The results showed that a high supply of provisioning services occurred in the oasis, while a high supply of regulating services existed in the high mountain region. The ES social demand was not completely accordant with the biophysical supply in spatial distribution, and the factors from the supply side and demand side could both cause ES supply-demand mismatches. The total well-being level of all indicators was higher in the oasis and desert than in the upstream areas (i.e., the high mountain region and low hills region), but some indicators (e.g., water consumption) were the inverse. The supply-demand mismatches in provisioning services had a strong impact on human well-being, while the supply-demand mismatches in regulating services had a low impact on human well-being. This can be explained by the ES social demand questionnaire results, which showed that the level of social importance was higher for provisioning services than for regulating services at our site. In accordance with our results, we recommended several policies to promote ecological conservation and improve human well-being in the Manas River Basin, and these policies could also be applied in other MOD areas. (C) 2018 Published by Elsevier B.V.