Tropospheric ozone (O3) pollution often accompanies droughts and heatwaves, which could collectively reduce plant productivity. Previous research suggested that O3 pollution can alter plant responses to drought by interfering with stomatal closure while drought can reduce stomatal conductance and provide protection against O3 stress. However, the interactions between O3 pollution and drought stress remain poorly understood at ecosystem scales with diverse plant functional types. To address this research gap, we used 10-year (2012−2021) satellite near-infrared reflectance of vegetation (NIRv) observations, reanalysis data of vapor pressure deficit (VPD), soil moisture (SM), and air temperature (Ta), along with O3 measurements and reanalysis data across the Northern Hemisphere to statistically disentangle the interconnections between NIRv, VPD, SM, and Ta under varying O3 levels. We found that high O3 concentrations significantly exacerbate the sensitivity of NIRv to VPD while have no notable impacts on the sensitivity of NIRv to Ta or SM for all plant functional types, indicating an enhanced combined impact of VPD and O3 on plants. Specifically, the sensitivity of NIRv to VPD increased by >75 % when O3 anomalies increased from the lowest 10 to the highest 10 percentiles across diverse plant functional types. This is likely because long-term exposure to high O3 concentrations can inhibit stomatal closure and photosynthetic enzyme activities, resulting in reduced water use efficiency and photosynthetic efficiency. This study highlights the need to consider O3 in understanding plant responses to climate factors and that O3 can alter plant responses to VPD independently of Ta and SM.