Populations in Central Asia are heavily dependent on snow and glacier melt for their water supplies. Changes to the glaciers in the main mountain range in this region, the Tien Shan, have been reported over the past decade. However, reconstructions over longer, multi-decadal timescales and the mechanisms underlying these variations—both required for reliable future projections—are not well constrained. Here we use three ensembles of independent approaches based on satellite gravimetry, laser altimetry, and glaciological modelling to estimate the total glacier mass change in the Tien Shan. Results from the three approaches agree well, and allow us to reconstruct a consistent time series of annual mass changes for the past 50 years at the resolution of individual glaciers. We detect marked spatial and temporal variability in mass changes. We estimate the overall decrease in total glacier area and mass from 1961 to 2012 to be 18 ± 6% and 27 ± 15%, respectively. These values correspond to a total area loss of 2,960 ± 1,030 km2, and an average glacier mass-change rate of −5.4 ± 2.8 Gt yr−1. We suggest that the decline is driven primarily by summer melt and, possibly, linked to the combined effects of general climatic warming and circulation variability over the north Atlantic and north Pacific.