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A systematic understanding of nitrous oxide (N₂O) emission and grain yield in winter wheat–summer maize rotation, one of the most important cereal cropping systems in China, is still lacking. The primary aim of this study was to quantify the N₂O emissions and grain yield, as well as responses to mitigation strategies, in this intensively managed agroecosystem. We conducted a pairwise meta-analysis by compiling a comprehensive dataset of annual N₂O emissions (<i>n</i> = 530) and grain yields (<i>n</i> = 352) from peer−reviewed publications. The N₂O emissions increased with nitrogen (N) fertilizer input rates following a linear model (r² = 0.295, <i>p</i> < 0.001), giving a specific emission coefficient and background emission of 0.71% and 0.5 kg N ha⁻¹ yr⁻¹, respectively. The grain yields responded to the N input rates following a linear-plateau model (r² = 0.478, <i>p</i> < 0.001), giving an optimal N input rate and maximum grain yield of 405 kg N ha⁻¹ yr⁻¹ and 15.5 t ha⁻¹ yr⁻¹, respectively. The meta-analyses revealed that reducing N fertilizers (approximately 50% of the full N input), water-saving irrigation, reduced or no tillage, and applying enhanced efficiency fertilizers significantly decreased N₂O emissions (range: −45% to −9%) and increased or did not impact grain yields (range: −1% to 3%). We recommend that reducing agricultural inputs (i.e., N fertilizers, irrigation, and tillage) is a feasible N₂O mitigation strategy in the intensively managed winter wheat–summer maize rotation that can be employed without additional environmental risks.