In this paper we assess the snow cover and its dynamics for the western river basins of the Indus River system (IRS) and their sub-basins located in Afghanistan, China, India and Pakistan for the period 2001–2012. First, we validate the Moderate Resolution Imaging Spectroradiometer (MODIS) daily snow products from Terra (MOD10A1) and Aqua (MYD10A1) against the Landsat Thematic Mapper/Enhanced Thematic Mapper plus (TM/ETM+) data set, and then improve them for clouds by applying a validated non-spectral cloud removal technique. The improved snow product has been analysed on a seasonal and annual basis against different topographic parameters (aspect, elevation and slope). Our results show a decreasing tendency for the annual average snow cover for the westerlies-influenced basins (upper Indus basin (UIB), Astore, Hunza, Shigar and Shyok) and an increasing tendency for the monsoon-influenced basins (Jhelum, Kabul, Swat and Gilgit). Seasonal average snow cover decreases during winter and autumn, and increases during spring and summer, which is consistent with the observed cooling and warming trends during the respective seasons. Sub-basins at relatively higher latitudes/altitudes show higher variability than basins at lower latitudes/middle altitudes. Northeastern and northwestern aspects feature greater snow cover. The mean end-of-summer regional snow line altitude (SLA) zones range from 3000 to 5000 m a.s.l. for all basins. Our analysis provides an indication of a descending end-of-summer regional SLA zone for most of the studied basins, which is significant for the Shyok and Kabul basins, thus indicating a change in their water resources. Such results are consistent with the observed hydro-climatic data, recently collected local perceptions and glacier mass balances for the investigated period within the UIB. Moreover, our analysis shows a significant correlation between winter season snow cover and the North Atlantic Oscillation (NAO) index of the previous autumn. Similarly, the inter-annual variability of spring season snow cover and spring season precipitation explains well the inter-annual variability of the summer season discharge from most of the basins. These findings indicate some potential for the seasonal stream flow forecast in the region, suggesting snow cover as a possible predictor.