CO2 emissions from Asian river systems represent a critical missing piece of information in the global riverine C budget. The rapid pace of urbanization across Asian river basins may affect riverine metabolic processes and CO2 emissions, adding a large uncertainty to the global C budget estimates. Synthesis of literature data was combined with exploratory field studies in three large Asian rivers (the Ganges, Mekong, and Yellow River) to explore how urbanization and associated water pollution affect the surface water partial pressure of CO2 (pCO2) via altered riverine metabolic processes along the hypothetical river continuum, which has long been used to explain longitudinal variations in “natural” riverine processes. In many Asian rivers including the three monitored rivers, pCO2 levels were much higher along the lower reaches and tributaries downstream of large metropolitan areas, compared to the relatively low pCO2 values observed in headwater systems. Reach-specific comparisons of dissolved organic matter (DOM) characteristics, including dissolved organic carbon (DOC) concentrations and stable isotope ratios, DOM optical intensities, and molecular signatures identified by ultrahigh resolution mass spectrometry, revealed strong influences of urban wastewater on the DOM composition in the lower reaches and tributaries. In-stream incubation experiments conducted with mainstem and polluted tributary waters in the Ganges (near Dhaka) and Mekong (along Phnom Penh) indicated stimulating effects of anthropogenic and planktonic DOM moieties on the biodegradation of DOM and CO2 emissions. The results suggest that high levels of water pollution in rapidly urbanizing river systems can shift the balance between autotrophy and heterotrophy in eutrophic river reaches toward a C-leaking state that might deviate drastically from the gradual longitudinal pattern assumed by the traditional river continuum concept.