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Nitrous oxide (N2O) is one of the most important climate-forcing gases, and a large portion of global anthropogenic N2O emissions come from agricultural soils. Yet, how contrasting global change factors and agricultural management can interact to drive N2O emissions remains poorly understood. Here, conducted within a rice–wheat cropping system, we combined a two-year field experiment with two pot experiments to investigate the influences of elevated atmospheric carbon dioxide (eCO2) and crop straw addition to soil in altering N2O emissions under wheat cropping. Our analyses identified consistent and significant interactions between eCO2 and straw addition, whereby eCO2 increased N2O emissions (+ 19.9%) only when straw was added, and independent of different N fertilizer gradients and wheat varieties. Compared with the control (i.e., ambient CO2 without straw addition), eCO2 + straw addition increased N2O emission by 44.7% and dissolved organic carbon to total dissolved nitrogen (DOC/TDN) ratio by 115.3%. Similarly, eCO2 and straw addition significantly impacted soil N2O-related microbial activity. For instance, the ratio of the abundance of N2O production genes (i.e., nirK and nirS) to the abundance of the N2O reduction gene (i.e., nosZ) with straw addition was 26.0% higher than that without straw under eCO2. This indicates an increased denitrification potential and suggests a change in the stoichiometry of denitrification products, affecting the balance between N2O production and reduction, leading to an increase in N2O emissions. Taken together, our results emphasize the critical role of the interaction between the specific agronomic practice of straw addition and eCO2 in shaping greenhouse gas emissions in the wheat production system studied, and underline the need to test the efficacy of greenhouse gas mitigation measures under various management practices and global change scenarios. [ABSTRACT FROM AUTHOR]