Two-year field experiments were conducted at Tamil Nadu Rice Research Institute, Aduthurai, Tamil Nadu, India, to evaluate the effect of continuous flooding (CF) and alternate wetting and drying (AWD) irrigation strategies on rice grain yield and greenhouse gas emissions from double-cropping paddy rice. Field observation results showed that AWD irrigation was found to reduce the total seasonal methane (CH4) emission by 22.3% to 56.2% compared with CF while maintaining rice yield. By using the observed two-year field data, validation of the DNDC-Rice model was conducted for CF and AWD practices. The model overestimated rice grain yield by 24% and 29% in CF and AWD, respectively, averaged over the rice-growing seasons compared to observed values. The simulated seasonal CH4 emissions for CF were 6.4% lower and 4.2% higher than observed values and for AWD were 9.3% and 12.7% lower in the summer and monsoon season, respectively. The relative deviation of simulated seasonal nitrous oxide (N2O) emissions from observed emissions in CF were 27% and −35% and in AWD were 267% and 234% in the summer and monsoon season, respectively. Although the DNDC-Rice model reasonably estimated the total CH4 emission in CF and reproduced the mitigation effect of AWD treatment on CH4 emissions well, the model did not adequately predict the total N2O emission under water-saving irrigation. In terms of global warming potential (GWP), nevertheless there was a good agreement between the simulated and observed values for both CF and AWD irrigations due to smaller contributions of N2O to the GWP compared with that of CH4. This study showed that the DNDC-Rice model could be used for the estimation of CH4 emissions, the primary source of GWP from double-cropping paddy rice under different water management conditions in the tropical regions.