AbstractDue to rapid population growth and the limitation of land resources, the sustainability of agricultural ecosystems has attracted more attention all over the world. Human activities will alter the components of the atmosphere and lead to climate change, which consequently affects crop production badly. In this context, wheat is considered an important crop and ranks as one of the top strategic crops globally. The main objective of this research is to develop a new approach (a weighted climatic suitability index) for evaluating the climate suitability for wheat production. The specific objectives are to project the impact of future climate change on wheat suitability using three models based on WCSI and CMIP6-based projections and to identify the most vulnerable area to climate change and productivity reduction. The climatic criteria for wheat production were selected and classified into eight indicators based on the Sys' scheme and the FAO framework, and then the weighted overlay approach was used in conjunction with the analytic hierarchy process. To confirm the reliability of the integrated WCSI, we determined the nonlinear curve fitting of integrated WCSI-induced wheat yields by the exponential growth equation. Finally, the CMIP6-GCMs projected from three shared socioeconomic pathways were used for WCSI mapping and predicting wheat yields in the short and long term (Southern Syria was selected as a case study). The results show that the nonlinear correlation between wheat yields and the integrated WCSI was 0.78 (R2 = 0.61) confirming the integrated WCSI's reliability in reflecting yield variation caused by climate suitability. The results indicated that WCSI for wheat will be lower over the study area during 2080–2100 compared to the current climate. During 2080–2100, the wheat yield is projected to decrease by 0.2–0.8 t. ha−1 in the western parts of the study area. The findings of this study could be used to plan and develop adaptation strategies for sustainable wheat production in the face of projected climate change. The results of the study will also help in the strategic planning of wheat production in Syria under the projected climate. The results of this research are limited to small areas as a case study, although they are not relevant to similar regions worldwide. However, the study employs novel analytical methods that can be used broadly.