We explore the climatic information contained in the record of length fluctuations of Glaciar Frías, in the North Patagonian Andes of Argentina. This record is one of the longest and most detailed glacier records in southern South America, starting in 1639. In order to interpret the length variations of Glaciar Frías since the maximum Little Ice Age extent in 1639, we use a combination of a simplified surface energy-balance model to calculate the glacier mass balance, and a flow-line model to account for the dynamical response of the glacier to changes in the climatic forcing. The overall retreat of the glacier observed over 1639–2009 is best explained by an annual mean temperature increase of 1.16 °C or a decrease in annual precipitation of 34%, most of which would have occurred during the 20th century. The glacier model is also forced with independent proxy-based reconstructions of precipitation and temperature, based on tree rings and a composition of documentary evidence, tree rings, sediments, corals, and ice cores. The uncertainties in the presently available proxy reconstructions are rather large, leading to a wide range in the modelled glacier length. Most of the observations lie within this range. However, in these reconstructions, the mid-17th century is too cold and the early 19th century ca. 0.7 °C too warm to explain the observed glacier lengths.