Rising global atmospheric carbon dioxide (CO) concentrations and surface temperatures could negatively affect rice yields and nutritional quality; however, their effects on arsenic accumulation in paddy rice have not been assessed concurrently. We aimed to assess the impact of increases in CO and temperature (individually and in combination) on arsenic concentrations in rice, characterise soil properties that might influence arsenic uptake, and model the associated risks of cancer and other health outcomes due to increased arsenic exposure. For this modelling study we performed in-situ multi-varietal trials using Free-Air CO Enrichment platforms with and without supplemental temperature to examine the bioaccumulation of arsenic in paddy rice and the underlying biogeochemical mechanisms from 2014 to 2023. We modelled dietary inorganic arsenic exposure and the associated risks of cancer and non-cancer health outcomes via rice consumption for seven of the leading rice-consuming countries in east and southeast Asia. Concomitant increases in CO and temperature resulted in a synergistic increase of inorganic arsenic in rice grain. The observed increase is likely to be related to changes in soil biogeochemistry that favoured reduced arsenic species. Modelled consumption of rice under these conditions resulted in projected increases in inorganic arsenic exposure and lifetime cancer and health risks for multiple Asian countries by 2050. Inorganic arsenic exposure and the associated health consequences might increase in rice grain grown in flooded systems with mid-century climate projections. The current assessment reinforces the urgent need for mitigation of arsenic exposure in rice relative to near-term climate change. National Key Research and Development Program of China, National Natural Science Foundation of China, Key-Area Research and Development Program of Guangdong Province, China, Carbon Peaking and Carbon Neutrality Special Fund for Science and Technology from Nanjing Science and Technology Bureau, Key Research and Development Program of Jiangsu Province, Erdos City Science and Technology Major Project, Science Foundation of the Chinese Academy of Sciences, Carbon Peaking and Carbon Neutrality Special Fund for Science and Technology from Jiangsu Science and Technology Department, and "0-1" Original Innovation Project of the Chinese Academy of Sciences.