Demand for rice will increase with growing global population. Globally, water management and nitrogen (N) application are two key factors influencing rice production and greenhouse gases (GHGs) emissions. In China, one of the world’s largest rice-producing countries, scarcity of water also threatens rice production. Therefore, in order to meet these challenges, it is essential to find water-use efficient irrigation management that also mitigates GHGs emissions from rice paddies. This study was conducted with three N application rates (90, 180, 270 kg N ha−1) under two irrigation regimes: 1) the conventional flooding-midseason drainage-flooding irrigation (FDF), and 2) flooding-moist by alternating wetting and drying (AWD) as the water-saving irrigation. Results showed that AWD irrigation significantly reduced CH4 emissions by 38%, but increased N2O emissions by 34%. Although N2O and CH4 emissions showed a trade-off relationship, the global warming potential (GWP) and greenhouse gas intensity (GHGI) significantly decreased by 22% and 24%, respectively, under water-saving irrigation management. N fertilization significantly enhanced rice grain yield but had no effects on water use efficiency (WUE). Although AWD had no effects on rice grain yield, it significantly enhanced WUE by 40%. Considering the interactive effects of N fertilization and irrigation management, the highest grain yield (7808.38 kg ha−1) occurred in AWD with medium N application rate. Generally, AWD irrigation regime could be used as an effective management for simultaneously saving water and enhancing rice grain yield, while mitigating GHGs emissions from rice paddies.