Recent controversy regarding the rates of disappearance of glaciers in the Himalayas, the world’s highest mountain chain, has primarily been focused on the eastern Himalayas. Studies carried out in the Central Karakoram Himalayan region suggest an expansion of glaciers. Little information exists about long-term glacier changes and their impact on streamflow in the Karakoram Himalayas where field surveys are difficult due to complex terrain and long term measurements have not been collected. The availability of global remotely sensed and climate datasets in the public domain provides an opportunity for studying large data sparse drainage basins. Following this approach, here I use remotely sensed datasets in combination with observational-based and simulated climate data to estimate glacier changes and their impact on streamflow variability in the Upper Indus Basin (UIB) located in the Karakoram Himalayas. Using Landsat images acquired between 1977 and 2006 and climate data from the Climate Research Unit (CRU), change detection analysis shows that the extent of perennial snow cover at higher elevations in the Central Karakoram has increased coinciding with a significant increase in winter precipitation and a decrease in summer temperature. Similarly, analysis of glacier thickness change estimated from the Ice, Cloud and Land Elevation Satellite (ICESat) altimeter data available between 2003 and 2008 with respect to the Shuttle Radar Topography Mission (SRTM) elevation data acquired in year 2000 identifies two clear patterns of change in the UIB. Strong thickening rates are observed within highly glacierized northern sub-watersheds (i.e. the Hunza and Shyok River basins), while thinning glaciers are identified in southern sub-watersheds. Statistically significant decreasing streamflow trends identified in all seasons for the Hunza River basin and increasing trends identified in other sub-basins of UIB for the period of 1974 – 2000 illustrate that observed streamflow response among sub-watersheds is closely related to the existence of distinct patterns in observed glacier changes. Trend analysis of water equivalence, snowmelt and glacier melt simulated using the Variable Infiltration Capacity (VIC) model, modified to represent glacier storage and melt, clarifies that increasing trends in ice and snow water equivalence and positive glacier thickening rates in the Hunza River basin decrease the melt contribution from higher altitude areas. Conversely, in other sub-basins increasing trends in streamflow are associated with increases in snow and ice melt contributions to the total streamflow. As a result of this study, an improved understanding of the governing factors of annual variability and timing of flows allow us to better assess the impacts of glaciers on streamflow in a changing climate. Additionally, the presented methodology for estimating glacier changes and their impact on streamflow requires relatively few data, mostly derived from global datasets. It therefore can be utilized for other data sparse drainage basins of the world