Barley is an important cereal crop for the arid and semi-arid Mediterranean environments. Future climate projections show that Mediterranean countries will get drier and hotter. The objectives of the study are to: i) simulate the impacts of different climate projections and different sowing dates on yield; ii) quantify the importance of heat and drought on barley yield at different growth stages and sowing dates; iii) quantify the contributions of sources of uncertainty among inter-annual variability, adaptation options and climate projections. Nine locations across the Mediterranean basin were used to calibrate and evaluate the Decision Support System for Agrotechnology Transfer (DSSAT) model. At each location the 40 Global Circulation Model (GCM) outputs (RCP4.5, Mid of the Century) showed an increase in mean growing season temperature between 0.9 and 2.16 °C, while changes of growing season rainfall were between -24 and +24%. Therefore, at each location a drier (Dry), mid (Mid), and wetter (Wet) projection was selected. Overall, there was a 9% reduction in grain yield under climate change; but the mean yield change was -27%, +4%, +8%, for the Dry, Mid, and Wet scenarios, respectively. The results of the simulations under the Wet scenario showed a higher variability of yield response. There was an interaction between the soil type, the amount of rainfall, the extractable soil water content and the maximum air temperature. Because of these relationship water-stress during the vegetative stage was experienced, affecting expansive growth. At the same time, the high number of days with Tmax>34 °C caused higher soil water depletion by the plant and therefore lower yields under the Wet scenario. The inter-annual weather variability impacts barley yield irrespective of the sowing dates and the future projected climate. In conclusion, the impact of future climate on barley yield in the Mediterranean is negative but some locations will be less affected than others.