Global projections of climate change indicate negative impacts on hydrological systems, with significant changes in precipitation and temperature in many parts of the world. As a result, floods and droughts are expected. This article discusses the potential effects of climate change and variability on the maximum precipitation, temperature, and hydrological regime in Devil’s Creek, Tacna, Peru. The outputs of precipitation and daily temperature of fifteen regional climate models were used for the RCP4.5 and RCP8.5 emission scenarios. The methodology used includes the bias correction and downscaling of meteorological variables using the quintiles mapping technique, hydrological modeling, the evaluation of two emission scenarios, and its effect on the maximum flows of the stream. The results of the multi-model ensemble show that the maximum annual precipitation will probably increase by more than 30% for the RCP4.5 and RCP8.5 scenarios for the 2021–2050 period relative to the 1981–2005 period. Likewise, as expected, the maximum flows could increase by 220% and 154% for the RCP4.5 scenarios for the 2021–2050 and 2051–2080 terms, respectively, and 234% and 484% for the RCP8.5 scenarios and for the 2021–2050 and 2051–2080 terms, respectively, concerning the recorded historical value, increasing the probability of flood events and damage in populations located downstream.