<p>As glaciers adjust their size in response to climate variations, long-term changes in meltwater production can be expected, affecting the local availability of water resources. We investigate glacier runoff in the period 1955–2016 in the Maipo River Basin (4 843 km<sup>2</sup>), semiarid Andes of Chile. The basin contains more than 800 glaciers covering 378 km<sup>2</sup> (inventoried in 2000). We model the mass balance and runoff contribution of 26 glaciers with the physically-oriented and fully-distributed TOPKAPI-ETH glacio-hydrological model, and extrapolate the results to the entire basin. TOPKAPI-ETH is run using several glaciological and meteorological datasets, and its results are evaluated against streamflow records, remotely-sensed snow cover and geodetic mass balances for the periods 1955–2000 and 2000–2013. Results show that glacier mass balance had a general decreasing trend as a basin average, but with differences between the main sub-catchments. Glacier volume decreased by one fifth (from 18.6 ± 4.5 to 14.9 ± 2.9 km<sup>3</sup>). Runoff from the initially glacierized areas was 186 ± 27 mm yr<sup>−1</sup> (17 ± 7 % of the total contributions to the basin), but it shows a decreasing sequence of maxima, which can be linked to the interplay between a decrease in precipitation since the 1980s and the reduction of ice melt. If glaciers in the basin were in equilibrium with the climate of the last two decades, their volume would be reduced to 81 ± 38 % of the year 2000 volume, and glacier runoff during dry periods would be 61 ± 24 % of its maximum contribution in the period 1955–2016, considerably decreasing the drought mitigation capacity of the basin.</p>