Climate change is increasing crop losses and yield variability with impacts for global food security. In this context, conservation agriculture appears as a potential solution to maintain crop productivity, soil fertility and environmental sustainability. Therefore, understanding the combined effects of soil tillage and crop succession over a long period is of primary interest. In this study, we analyzed data from a 50 year long-term field experiment to assess (i) the change of climatic parameters, wheat yield and soil organic carbon (SOC) content; (ii) the combined effects of crop succession (monoculture vs. crop rotation) and soil tillage system (minimum tillage vs. plough) on wheat yield, SOC content and other soil properties at three soil depths (0-10, 10-20 and 20-50 cm); and (iii) the relative contributions of climatic parameters, wheat phenology and agricultural practices on wheat yield variability. Wheat yield was 16% higher in crop rotation compared to monoculture, while soil tillage system had no significant effect on wheat yield during the period 1977-2016. Despite a SOC content decline over time, which was especially marked during the first ten years of the study, SOC content was 7% higher in the minimum tillage treatment compared to the plough treatment, while crop rotation had no significant effect. In 2016, after 50 years of experimentation, both crop succession and soil tillage systems influenced soil properties. Over the 50-year period, the climatic conditions around the heading phase explained 22% of yield variability, while 18% of this variability was explained by crop succession and 6% by the growing degree days until heading stage. In a context of conservation agriculture promotion, our long-term field experiment provides key evidence that the combination of both minimum soil tillage and crop rotation improves soil fertility and crop productivity.