The pressing issue of increasing tropospheric ozone (O-3) levels necessitates the development of effective stress management strategies for plant protection. While considerable research has elucidated the adverse impacts of O-3, understanding the combined effects of O-3 and CO2 requires further investigation. This study focuses on assessing the response of stomatal O-3 flux under various O-3 and CO2 treatments, individually and in combination, and their repercussions on physiological, growth, and yield attributes in two Indian wheat cultivars, HUW-55 and PBW-550, which exhibit varying levels of sensitivities against elevated O-3. Results indicated significant alterations in stomatal O-3 flux in both O-3-sensitive and tolerant wheat cultivars across different treatments, influencing the overall yield outcomes. Particularly, the ECO2+EO3 treatment demonstrated more positive yield protection in the O-3-sensitive cultivar PBW-550, compared to HUW-55 indicating enhanced allocation of photosynthates towards reproductive development in PBW-550, compared to the tolerant cultivar HUW-55, as evidenced by higher harvest index (HI). Furthermore, the study revealed a stronger correlation between yield response and stomatal O-3 flux in PBW-550 (R-2 = 0.88) compared to HUW-55 (R-2 = 0.79), as indicated by a steeper regression slope for PBW-550. The research also confirmed the role of elevated CO2 in reducing stomatal O3- flux in the tested cultivars, with discernible effects on their respective yield responses. Further experimentation is necessary to confirm these results across different cultivars exhibiting varying sensitivities to O-3. These findings can potentially revolutionize agricultural productivity in regions affected by O-3 stress. The criteria for recommending cultivars for agricultural practices should not be based only on their sensitivity/tolerance to O-3. Still, they should also consider the effect of CO2 fertilization in the growing area. This experiment offers hope to sustain global food security, as the O-3-sensitive wheat cultivar also showed promising results at elevated CO2. In essence, this research could pave the way for more resilient agricultural systems in the era of changing climate under elevated O-3 and CO2 conditions.