Cropland ecosystems are significant emission sources of N2O, but a limited number of studies have focused on the impact of extreme weather events on N2O fluxes from cropland. This present study integrated field observations and model simulations to explore the responses of N2O fluxes to extreme weather events in typical rice and wheat rotation croplands in the middle and lower reaches of the Yangtze River (MLRYR) in China. The findings revealed that the studied rice-wheat rotation cropland exhibited a net source of N2O over the three-year monitoring period, with annual cumulative N2O emissions ranging from 190.4 to 261.8 mg N m−2. N2O emissions during the rice and wheat growing seasons accounted for 29% and 71% of the total yearly emissions, respectively. Extreme heat events led to a 23% to 32% increase in observed N2O emissions from cropland. Observed N2O emissions from irrigated rice fields during extreme precipitation events were 45% lower than those during extreme drought events. In contrast, extreme precipitation events raised observed N2O emissions from rain-fed wheat fields by 36% compared to the multi-year average, while extreme drought events reduced N2O emissions from wheat fields by 20%. Regional simulations indicated that annual cumulative N2O emissions from croplands in the MLRYR are projected to increase from 207.8 mg N m−2 under current climate to 303.4 mg N m−2 in the future. Given the episodic nature and uncertainties associated with N2O emissions from cropland, further validation is necessary for utilizing the model to explore the effects of extreme weather events on N2O in cropland ecosystems.