Drought events are critical environmental threats that yield several socioeconomic impacts. Such effects are even more relevant for South America (SA) since different activities essential for the continent, such as agriculture and energy generation, depend highly on water resources. Thus, this study aimed to evaluate future changes in precipitation and hydrological drought occurrence in SA through climate projections from eight global climate models (GCMs) of CMIP6. To this end, statistical downscaling was applied to the projections obtained using the quantile delta mapping technique, and the method proved to be efficient in reducing systematic biases and preserving GCMs’ trends. For the following decades, the results show considerable and statistically significant reductions in precipitation over most of SA, especially during the austral spring, with the most intense signal under the SSP5-8.5 forcing scenario. Furthermore, GCMs showed mixed signals about projections of the frequency and intensity of drought events. Still, they indicated agreement regarding the increased duration and severity of events over the continent and a substantial proportion of moderate and severe events over most of Brazil during the 21st century. These results can be helpful for better management of water resources by decision-makers and energy planners.