Wheat is grown in the largest area in the world as well as in Hungary. Globally, the yield is predicted to decrease due to climate change; however, technological development can potentially compensate for it. In this study, the contribution of climatic and technological trends to the change in winter wheat yield in four sub-regions of Hungary with considerable spatial and temporal variations in weather conditions was evaluated. Long-term trends in both the weather conditions and the technology development, with the consideration of the socio-economic circumstances, were identified. For future yield prediction, non-climatic influences and critical climatic factors, as well as sensitivity in the phenological stages, were considered. In the past 50 years, the average yield variation was lower at regional than country scale. Winter wheat yield was not found to be sensitive to temperature, global degree days, precipitation, and climatic water balance, only to heat stress. Considering the technological development and the heat stress during the critical weeks in the last 30 years, an increase of yields can be expected by 2050 in Hungary’s western regions (0.72–1.55 t ha−1), while yield depression is predicted (0.27–0.75 t ha−1) in the eastern regions compared to the values estimated for 2019, ±1.5 t ha−1 within a 95% confidence interval. We proved that yield estimations can show contradictory changes by sub-regions of an agricultural region if the contribution of site-specific technology development, the dominant weather stressor, and the most sensitive phenological phase is involved in the statistical analyses. Identification of the dominant climatic stressor(s) for the different crops is necessary to keep high yield or even increase it under the changing environmental circumstances. Our findings suggest that heat stress is the main concern to maximize winter wheat production in temperate climate zones.