Satisfying human food demands without degrading natural capital under climate change comprises one of the grandest challenges in the 21st century. Crop substitution - the process of replacing one crop with another crop, is an effective measure for adapting climate change, which helps to address this issue. The objective of this research is examining the potential of crop substitution based on climate changes to improve agri-food production, environmental stewardship and regional prosperity in China. First, we harness climate, crop, agricultural inputs and cost-benefits data of 2031 counties from 1981 to 2017 and project the crop yield and land-use climate suitability based on future climate projections. Second, we develop and invoke a conceptual framework of crop substituting based on maize (a crop requiring high nitrogen amounts) and soybean (a more sustainable crop but with lower productivity), which integrate demand, impacts of climate change on yield, crop land-use climate suitability, high- or low-yield and soybean-based rotation co-benefits to adapt future climate change. Finally, we scale these findings to compute implications for national environmental impacts and economic profit. After substitution, national soybean production would reach 37.2 Mt. in 2021–2060 when maize production meet demand, avoiding 4.0 Mt. reduction in production losses associated with climate change. Nitrogen fertilizer use and net greenhouse gas emissions would reduce by 21.5–24.6 and 7.9–8.7%, respectively, increasing soybean and maize economic profit by 46.1–49.3%. Our findings will help the policy makers for safeguarding food security under future climate in China. The conceptual framework of crop substituting we developed here would help to come up with suitable crop planting area programme to adapt climate change, and increase productivity, environmental stewardship and regional prosperity.