Throughout the second half of the 20th century, the Central Andes has experienced significant climatic and environmental changes characterized by a persistent warming trend, an increase in elevation of the 0 °C isotherm, and sustained glacier shrinkage. These changes have occurred in conjunction with a steadily growing demand for water resources. Given the short span of instrumental hydroclimatic records in this region, longer time span records are needed to understand the nature of climate variability and to improve the predictability of precipitation, a key factor modulating the socio-economic development in the South American Altiplano and adjacent arid lowlands. In this study we present the first quasi-millennial, tree-ring based precipitation reconstruction for the South American Altiplano. This annual (November-October) precipitation reconstruction is based on the Polylepis tarapacana tree-ring width series and represents the closest dendroclimatological record to the Equator in South America. This high-resolution reconstruction covers the past 707 yr and provides a unique record characterizing the occurrence of extreme events and consistent oscillations in precipitation. It also allows an assessment of the spatial and temporal stabilities of the teleconnections between rainfall in the Altiplano and hemispheric forcings such as El Niño-Southern Oscillation. Since the 1930s to present, a persistent negative trend in precipitation has been recorded in the reconstruction, with the three driest years since 1300 AD occurring in the last 70 yr. Throughout the 707 yr, the reconstruction contains a clear ENSO-like pattern at interannual to multidecadal time scales, which determines inter-hemispheric linkages between our reconstruction and other precipitation sensitive records modulated by ENSO in North America. Our reconstruction points out that century-scale dry periods are a recurrent feature in the Altiplano climate, and that the future potential coupling of natural and anthropogenic-induced droughts may have a severe impact on socio-economic activities in the region. Water resource managers must anticipate these changes in order to adapt to future climate change, reduce vulnerability and provide water equitably to all users.