The Amazon region, being a large source of methane (CH4), contributes significantly to the global annual CH4 budget. For the first time, a forward and inverse modelling framework on regional scale for the purpose of assessing the CH4 budget of the Amazon region is implemented. Here, we present forward simulations of CH4 as part of the forward and inverse modelling framework based on a modified version of the Weather Research and Forecasting model with chemistry that allows for passive tracer transport of CH4, carbon monoxide, and carbon dioxide (WRF-GHG), in combination with two different process-based bottom-up models of CH4 emissions from anaerobic microbial production in wetlands and additional datasets prescribing CH4 emissions from other sources such as biomass burning, termites, or other anthropogenic emissions. We compare WRF-GHG simulations on 10 km horizontal resolution to flask and continuous CH4 observations obtained during two airborne measurement campaigns within the Balanço Atmosférico Regional de Carbono na Amazônia (BARCA) project in November 2008 and May 2009. In addition, three different wetland inundation maps, prescribing the fraction of inundated area per grid cell, are evaluated. Our results indicate that the wetland inundation maps based on remote-sensing data represent the observations best except for the northern part of the Amazon basin and the Manaus area. WRF-GHG was able to represent the observed CH4 mixing ratios best at days with less convective activity. After adjusting wetland emissions to match the averaged observed mixing ratios of flights with little convective activity, the monthly CH4 budget for the Amazon basin obtained from four different simulations ranges from 1.5 to 4.8 Tg for November 2008 and from 1.3 to 5.5 Tg for May 2009. This corresponds to an average CH4 flux of 9–31 mg m−2 d−1 for November 2008 and 8–36 mg m−2 d−1 for May 2009