Abstract: Elevated CO₂ concentrations can modify evapotranspiration processes by increasing surface resistance, affecting changes in dryness and wetness. Consequently, it is imperative to undertake a comprehensive examination of the physiological impact of CO₂ on vegetation, aiming to elucidate the underlying mechanisms governing changes in dryness and wetness. This study comprehensively analyzed the changes in dryness and wetness over the Huai River Basin from 1965 to 2020. The analysis was based on the improved FAO-56 (Food and Agriculture Organization-56) Penman–Monteith equation, incorporating the physiological effect of CO₂ on vegetation and the self-calibrated Palmer Drought Severity Index. Furthermore, a joint-solution method with multiple sensitivity experiments was employed to quantify the impacts of different influential factors on the changes in dryness and wetness, thereby revealing the underlying mechanisms. Results indicated that over the past 56 years, the Huai River Basin, along with more than 51% of the regions, has undergone significant (p＜0.05) wetting on annual and seasonal (excluding spring) time scales. The annual wetting trends in the study region can be attributed to increased precipitation. However, the seasonal dominant factors for these wetting trends differ, primarily characterized by a decline in wind speed in spring but increased precipitation in the other seasons. Geographically, wind speed dominated 52.7% of the areas in spring. In comparison, precipitation significantly contributed to the dryness/wetness over more than 57% of the areas on an annual basis and during the other three seasons.