Ensuring global food security requires a sound understanding of climate and environmental controls on crop productivity. The majority of existing assessments have focused on physical climate variables (i.e., mean temperature and precipitation), but less on the increasing climate extremes (e.g., drought) and their interactions with increasing levels of tropospheric ozone (O₃). Here we quantify the combined impacts of drought and O₃ on China's crop yield using a comprehensive, process-based agricultural ecosystem model in conjunction with observational data. Our results indicate that climate change/variability and O₃ together led to an annual mean reduction of crop yield by 10.0% or 55 million tons per year at the national level during 1981–2010. Crop yield shows a growing threat from severe episodic droughts and increasing O₃ concentrations since 2000, with the largest crop yield losses occurring in northern China, causing serious concerns in food supply security in China. Our results imply that reducing tropospheric O₃ levels is critical for securing crop production in coping with increasing frequency and severity of extreme climate events such as droughts. Improving air quality should be a core component of climate adaptation strategies.