Rice production is a substantial source of atmospheric CH4, which is second only to CO2 as a contributor to global warming. Since CH4 is produced in anaerobic soil environments, water management is expected to be a practical measure to mitigate CH4 emissions. In this study, we used a process-based biogeochemistry model (DNDC-Rice) to assess the CH4 mitigation potentials of alternative water regimes (AWR) for rice fields at a regional scale. Before regional application, we tested DNDC-Rice using site-scale data from three rice fields in Japan with different water regimes. The observed CH4 emissions were reduced by drainage of the fields, but were enhanced by organic amendments. DNDC-Rice gave acceptable predictions of variation in daily CH4 fluxes and seasonal CH4 emissions due to changes in the water regime. For regional application, we constructed a GIS database at a 1 × 1 km mesh scale that contained data on rice field area, soil properties, daily weather, and farming management of each cell in the mesh, covering 3.2% of the rice fields in Japan's Hokkaido region. We ran DNDC-Rice to simulate CH4 emissions under five simulated water regimes: the conventional water regime and four AWR scenarios with gradually increasing drainage. We found that AWR can reduce CH4 emission by up to 41% compared with the emission under conventional water regime. Including the changes in CO2 and nitrous oxide emissions, potential mitigation of greenhouse gas (GHG) was 2.6 Mg CO2 Eq. ha−1 yr−1. If this estimate is expanded to Japan's total rice fields, expected GHG mitigation is 4.3 Tg CO2 Eq. yr−1, which accounts for 0.32% of total GHG emissions from Japan. For a reliable national-scale assessment, however, databases on soil, weather, and farming management must be constructed at a national scale, as these factors are widely variable between regions in Japan.