Oxygen (O2) plays a critical and yet poorly understood role in regulating nitrous oxide (N2O) production in well-structured agricultural soils. We investigated the effects of in situ O2 dynamics on N2O production in a typical intensively managed Chinese cropping system under a range of environmental conditions (temperature, moisture, ammonium, nitrate, dissolved organic carbon, and so forth). Climate and management (fertilization, irrigation, precipitation, and temperature), and their interactions significantly affected soil O2 and N2O concentrations (P < 0.05). Soil O2 concentration was the most significant factor correlating with soil N2O concentration (r = -0.71) when compared with temperature, water-filled pore space, and ammonium concentration (r = 0.30, 0.25, and 0.26, respectively). Soil N2O concentration increased exponentially with decreasing soil O2 concentrations. The exponential model of N treatments and fertilization with irrigation/precipitation events predicted 74-90% and 58% of the variance in soil N2O concentrations, respectively. Our results highlight that the soil O2 status is the proximal, direct, and the most decisive environmental trigger for N2O production, outweighing the effects of other factors and could be a key variable integrating the aggregated effects of various complex interacting variables. This study offers new opportunities for developing more sensitive approaches to predicting and through appropriate management interventions mitigating N2O emissions from agricultural soils.