This study characterizes the future changes in extreme rainfall and air temperature in the Mono river basin where the main economic activity is weather dependent and local populations are highly vulnerable to natural hazards, including flood inundations. Daily precipitation and temperature from observational datasets and Regional Climate Models (RCMs) output from REMO, RegCM, HadRM3, and RCA were used to analyze climatic variations in space and time, and fit a GEV model to investigate the extreme rainfalls and their return periods. The results indicate that the realism of the simulated climate in this domain is mainly controlled by the choice of the RCMs. These RCMs projected a 1 to 1.5 °C temperature increase by 2050 while the projected trends for cumulated precipitation are null or very moderate and diverge among models. Contrasting results were obtained for the intense rainfall events, with RegCM and HadRM3 pointing to a significant increase in the intensity of extreme rainfall events. The GEV model is well suited for the prediction of heavy rainfall events although there are uncertainties beyond the 90th percentile. The annual maxima of daily precipitation will also increase by 2050 and could be of benefit to the ecosystem services and socioeconomic activities in the Mono river basin but could also be a threat.