This study examines the projections of hydroclimatic regimes and extremes over Andean basins in central Chile (∼ 30–40 S). We have used daily precipitation and temperature data based on observations to drive and validate the VIC macro-scale hydrological model in the region of interest at a 0.25 × 0.25 degree resolution. Historical (1960–2005) and projected, following the RCP8.5 scenario (2006–2099), daily precipitation and temperatures from 26 CMIP5 climate models are bias corrected and used to drive the VIC model to obtain regional hydroclimate projections. Following the robust drying and warming shown by CMIP5 models in this region, the VIC model simulations indicate decreases in annual runoff of about 40 % by the end of the century, larger that the projected precipitation decreases (up to 30 %). Center timing of runoff shifts to earlier dates, 3–5 weeks by the end of the century. The Andes snowpack is projected to be less than half of the reference period by mid-century. The projected hydroclimatic regime is also expected to increase the severity and frequency of extreme events. The probability of having extended droughts, such as the recently experienced mega-drought (2010–2015), increases to up to 5 events/100 years. On the other hand, probability density function of annual maximum daily runoff indicates an increase in the frequency of flood events. The estimated return periods of annual maximum runoff events depict more drastic changes and increase in the flood risk as longer return periods are considered (e.g. 25-yr and 50-yr).