Ganges and Brahmaputra, two of Asia’s most prominent rivers, have a crucial role in Southeast Asia’s geopolitics and economy and are home to one of the world’s biggest marine ecosystems. Irrigation-driven groundwater depletion and climate change affect the Ganges-Brahmaputra’s hydrology, threatening the stability of the Bay of Bengal. Here, we quantify, using results from a land reanalysis, the impacts of a changing climate and intensive irrigation on the surface water flowing into the Bay of Bengal. The effects of such activities mostly occurring in the Ganges basin, either intensified or lessened depending on the area by the climatic conditions, decrease freshwater flow into the bay by up to 1200 m3/s/year. While the increase in precipitation in the Ganges basin reduces the effects of groundwater depletion on the streamflow, the decrease in precipitation and the snowmelt decline in the Brahmaputra basin exacerbate streamflow reduction due to groundwater depletion at the delta.