Anthropogenic perturbations are increasing uncertainties in estimating CO2 emissions via air-water CO2 flux (FCO2) from large rivers of the Indian subcontinent. This study aimed to provide an improved estimate of the total FCO2 from the subcontinental rivers by combining calculations of the partial pressure of CO2 (pCO2) in eight major rivers with new measurements in the Ganges and Godavari. The average pCO2 in the two newly surveyed rivers, including tributaries, wastewater drains, and impoundments, were 3–6 times greater than the previously reported values. In some highly polluted urban tributaries and middle reaches of the Ganges that drain metropolitan areas, the measured pCO2 exceeded 20,000 μatm, ~40 times the background levels of the headwaters originating in the carbonate-rich Himalayas. The high pCO2 above 28,000 μatm in the lower reach of the Godavari was seven times the moderate levels of pCO2 in the headwaters of the volcanic Deccan Traps, indicating enhanced CO2 production in soils and anthropogenic sources under favorable conditions for organic matter degradation. Across the northern rivers, pCO2 exhibited a significant negative relationship with dissolved oxygen, but a positive relationship with inorganic N or P concentrations. The strong influence of water pollution on riverine pCO2 suggests that CO2 emissions from hypoxic, eutrophic reaches can greatly exceed phytoplanktonic CO2 uptake. Spatially resolved pCO2 data, combined with three gas transfer velocity estimates, provided a higher range of FCO2 from the subcontinental rivers (100.9–130.2 Tg CO2 yr−1) than the previous estimates (7.5–61.2 Tg CO2 yr−1). The revised estimates representing 2–5% of the global riverine FCO2 illustrate the importance of the Indian subcontinental rivers under increasing anthropogenic pressures in constraining global inland waters FCO2.