Climate change in Central Europe is expected to influence crop growth through frequent drought and heat extremes. Wheat contributing about 20% of the total dietary calories and proteins worldwide, is sensitive to heat and drought, especially during its reproductive stages. To develop strategies to improve climate resilience in wheat, a comprehensive field evaluation was carried out under drier and warmer field conditions in Moldova from 2016 to 2019 for forty winter wheat varieties from Germany and Eastern Europe. The grain yield of German cultivars grown in Moldova ranged from 4.46–6.58 t/ha from 2016 to 2019 and was 40% lower compared to the same cultivars grown in Southern Germany. This is significantly more than the reduction predicted by current process-based crop yield models considering only seasonal temperature effects and not combined drought effects. Among all the wheat varieties tested in Moldova, Eastern European varieties and German hybrids achieved the best yield performance across the years. The lower grain yield of German wheat varieties was mainly due to the reduction in grain filling duration, which led to a decrease in the grain filling rate and thousand-grain weight. A higher grain filling rate contributed to a higher grain yield in the Eastern European varieties. These results suggest that well-adapted varieties with a faster rate of development and an earlier start of grain filling have a notable advantage under drought and heat conditions, providing a useful genetic source to increase heat and drought tolerance in future plant breeding programs. The space-for-time approach used in this study allows for the investigation of combined heat and drought, reflecting anticipated or future climate conditions without taking into account CO₂ effects.