Despite growing research on greenhouse gas (GHG) emissions from inland waters, few systematic efforts have been made to assess the regional-scale GHG emissions from Asian rivers under increasing anthropogenic stress. We examined factors controlling longitudinal and seasonal variations in the partial pressure of CO2 (pCO2), and CH4 and N2O concentrations in the Ganges, Mekong, and Yellow River by simultaneously measuring gas concentrations and stable C isotopes, and optical properties of dissolved organic matter (DOM) from 2016 to 2019. The levels of pCO2 and CH4 were distinctively higher in polluted tributaries and affected reaches of the Ganges and Mekong than in the Yellow River. The highest levels of N2O were found in the Ganges, followed by the Yellow River and Mekong. Across these basins, dry-season mean concentrations of CO2, CH4, and N2O were 1.6, 2, and 7 times higher than those measured in the monsoon season, respectively. This seasonality was consistent with that of δ13C-CO2, while δ13C-CH4 showed an opposite pattern. GHG concentrations exhibited significant positive relationships with DOM concentrations and optical properties including fluorescence index and protein-like fluorescence, implying the contribution of anthropogenic, labile DOM to production of GHGs in the polluted reaches. Graphical mixing models of δ13C-CO2 and δ13C-CH4 support the stronger impact of wastewater on the Ganges and Mekong than on the Yellow River. The overall results suggest that neglecting localized pollution impacts on GHG emissions from increasingly urbanized river basins can result in a substantial underestimation of global riverine GHG emissions.