Climate change in Mediterranean countries is anticipated to have a strong impact on water availability by exacerbating drought conditions and water scarcity. In this context, efficient irrigation practices are becoming essential for sustaining crop production. This work assesses vulnerability of irrigated agriculture for six irrigation districts and their associated reservoirs in Mediterranean areas across Italy under climate change (1976–2005 versus 2036–2065; RCP 4.5 and 8.5), evaluating changes in irrigation requirements, evaporation from reservoirs, and the availability of freshwater supplies. Irrigation requirements are estimated through a crop water model (SIMETAW_R) integrated into a GIS platform, while inflows to reservoirs are hydrologically modelled as partitioning of precipitation contributing to runoff. Results are aggregated into indicators that show the general decreasing resilience and increasing vulnerability of irrigated agriculture under climate change conditions in each case study. The highest percentage of allowable water losses for irrigation is estimated in the Cuga-Alto Temo system, during the prolonged drought period, to be able to satisfy irrigation demand for less than a year. Climate change may only partially affect irrigation in resilient systems, in which storage capacity and the water level entering into the reservoir are considerably higher than the water distribution volumes.