Coastal areas dominated by major rivers are one of the largest carbon sinks worldwide. However, the factors controlling the generation of primary microbial gas therein are still poorly understood. Here, the geochemical characteristics of natural gas and organic-rich muds (organofacies) from the upper Quaternary delta–shelf–estuary system that links the large Changjiang and the adjacent smaller Qiantang River are investigated to understand the key factors controlling the preservation of organic matter and its gas-generation potential. Muds from the floodplain, salt marshes of the paleoestuary, and distal delta front and prodelta of the paleodelta act as efficient gas-generation organofacies. Organic matter in them consists mainly of terrestrial higher land plants and is now undergoing methanogenesis. These organofacies were deposited during transgression accompanied by an intensified Asian summer monsoon that resulted in a greater delivery of organic matter and a higher preservation efficiency and reactivity of organic carbon compared to the subsequent regressive organofacies. Notably, the factors influencing the gas-generation potential in this system varied in a proximal–distal direction. Energetic physical processes acting during the accumulation of the distal delta-front and prodeltaic muds resulted in a longer oxygen exposure time, repetitive redox oscillations, and replenishment of labile marine organic matter, which accelerated microbial degradation before methanogenesis began. Our findings thus suggest that the most efficient gas-generation organofacies in a large river-dominated delta–shelf–estuary system are those deposited in a proximal environment, especially under conditions of rapid aggradation during times of sea-level rise and increased runoff associated with a warm climate.