Climate change is expected to alter the conditions in which plants develop. The mechanisms by which plants can adapt to changing conditions must be studied in terms of the magnitude of their response and the implications for productivity. Recognizing wheat as a main crop sustaining global livelihoods as well as the need for long-term adaptation strategies to climate change, this work assesses the response of wheat stomatal conductance (gs) to changes in vapor pressure deficit (VPD) associated with global warming in three future scenarios from the Coupled Model Inter-comparison Project phase 6 (CMIP6). We used multiple datasets and a modeling approach to estimate gs as a function of atmospheric variables only over global wheat areas. The results show a sustained increase in both temperature and VPD in the historical period and future CMIP6 scenarios, and a generalized decrease in wheat gs that becomes clear from around the year 2040. The pattern of change is spatially divergent, with areas that present increases in relation to the historical average, which mostly concentrate towards high latitudes. Negative trends in gs area mainly observed in North America, Southern Europe, North Africa and Asia. Notwithstanding, the proportion of areas of positive change in gs tend to decrease in warmer climate scenarios. gs is more sensitive to changes in VPD than to global warming, which implies that the areas of negative trends in gs could expand to higher latitudes. These results may assist the regional focus of long-term wheat adaptation programs to climate change.