Ozone pollution is a growing problem in many developing countries posing challenges not only to air quality but also affecting agricultural productivity and human well-being. This is the first study in the Indo-Gangetic Plain exploring how the spatial variation and severity of tropospheric ozone affect both wheat yield and all-cause mortality. We estimated that ozone-related cumulative crop production loss for wheat in selected districts of IGP was 3.4 million tonnes during the study period (2019–2021), which amounted to 923 million USD. The production-weighted Relative Yield Loss (RYL) for wheat in the IGP was 9.3 % in 2019, 12.8 % in 2020, and 11.3 % in 2021. The losses incurred in 2021 could contribute to fulfilling the wheat requirements of 11.4 million people. We also assess the health and economic gains resulting from the attainment of the World Health Organization Air Quality Guidelines (WHO AQG) for ozone concentrations. It is estimated that interventions that achieve AQG would have averted 11,407 premature deaths in 2021 translating into an impressively large health and economic gain. The annual benefits in 2021 totaled to 34 billion USD. We observe that Uttar Pradesh experienced the highest losses, both in terms of crop damage and premature deaths. Our study observes that implementing policies to prepone the planting of wheat enhances food security by mitigating yield losses. Mitigating the health impact of ambient ozone necessitates a reduction in anthropogenic emissions and to attain this objective, we propose adopting an exposure-integrated source reduction approach.