The impact of climate change on drought main characteristics was assessed over Southern South America. This was done through the precipitation outputs from a multi-model ensemble of 15 climate models of the Coupled Model Intercomparison Project Phase 5 (CMIP5). The Standardized Precipitation Index was used as a drought indicator, given its temporal flexibility and simplicity. Changes in drought characteristics were identified by the difference for early (2011-2040) and late (2071-2100) 21st century values with respect to the 1979-2008 baseline. In order to evaluate the multi-model outputs, model biases were identified through a comparison with the drought characteristics from the Global Precipitation Climatology Centre database for the baseline period. Future climate projections under moderate and high-emission scenarios showed that the occurrence of short-term and long-term droughts will be more frequent in the 21st century, with shorter durations and greater severities over much of the study area. These changes in drought characteristics are independent on the scenario considered, since no significant differences were observed on drought changes. The future changes scenario might be even more dramatic, taking into account that in most of the region the multi-model ensemble tends to produce less number of droughts, with higher duration and lower severity. Therefore, drought contingency plans should take these results into account in order to alleviate future water shortages that can have significant economic losses in the agricultural and water resources sectors of Southern South America.