Wheat is an important staple crop sensitive to negative effects from elevated tropospheric ozone (O3) concentrations, but the impacts of future O3 concentrations on wheat production in Mexico are unknown. To determine these impacts, the O3-modified DSSAT-NWheat crop model was used to simulate wheat production in Mexico using a baseline scenario with pre-industrial O3 concentrations from 1980 to 2010 and five Global Climate Models (GCMs) under the Representative Concentration Pathway (RCP) 8.5 scenario from 2041 to 2070 paired with future O3 concentrations from the European Monitoring and Evaluation Programme (EMEP) Meteorological Synthesizing Centre–West (MSC-W) model. Thirty-two representative major wheat-producing locations in Mexico were simulated assuming both irrigated and rainfed conditions for two O3 sensitivity cultivar classifications. The simulations showed large variability (after averaging over 30 years) in yield loss, ranging from 7 to 26% because of O3impact, depending on the location, irrigation, and climate change emissions scenario. After upscaling and aggregating the simulations to the country scale based on observed irrigated and rainfed production, national wheat production for Mexico is expected to decline by 12% under the future RCP 8.5 climate change scenario with additional losses of 7 to 18% because of O3impact, depending on the cultivar O3 sensitivity. This yield loss caused by O3 is comparable with, or even larger than, the impact from projected future climatic change in temperature, rainfall, and atmospheric CO2 concentration. Therefore, O3 impacts should be considered in future agricultural impact assessments.