The spatiotemporal variability of the greenhouse gas methane (CH4) in the atmosphere over the Amazon is studied using data from the space-borne measurements of the Atmospheric Infrared Sounder on board NASA’s AQUA satellite for the period 2003–12. The results show a pronounced variability of this gas over the Amazon Basin lowlands region, where wetland areas occur. CH4 has a well-defined seasonal behavior, with a progressive increase of its concentration during the dry season, followed by a decrease during the wet season. Concerning this variability, the present study indicates the important role of ENSO in modulating the variability of CH4 emissions over the northern Amazon, where this association seems to be mostly linked to changes in flooded areas in response to ENSO-related precipitation changes. In this region, a CH4 decrease (increase) is due to the El Nino-related (La Nina-related) dryness (wetness). On the other hand, an increase (decrease) in the biomass burning over the southeastern Amazon during very dry (wet) years explains the increase (decrease) in CH4 emissions in this region. The present analysis identifies the two main areas of the Amazon, its northern and southeastern sectors, with remarkable interannual variations of CH4. This result might be useful for future monitoring of the variations in the concentration of CH4, the second-most important greenhouse gas, in this area.