High-frequency, paired measurements of the partial pressure of CO2 (pCO2) and dissolved O2 were combined with dissolved organic matter (DOM) characterization to investigate diurnal (7:00–19:00) and seasonal variations in CO2 dynamics in the lower Ganges River. Diurnal variations in pCO2 shifted seasonally, concurring with changes in DOM optical properties, biodegradable DOM, and O2 departures from atmospheric equilibrium (ΔO2). Increased pCO2 and CO2 flux (FCO2) in August–September corresponded to monsoonal floods carrying more terrestrial materials. Lower dry-season pCO2 and FCO2 concurred with higher ΔO2, and exhibited strong relationships with DO and pH, indicating a dominant influence of phytoplankton production. Despite large variations in pCO2, the year-long positive FCO2 implied that the lower Ganges acted as a CO2 source, reaching 122 mmol m−2 d−1. Increasing hydrologic variability and pollution in the Ganges Basin can amplify pCO2 variations linked to seasonal shifts in terrestrial inputs and phytoplankton production.