Damming is one of the major methods that human being secure reliable freshwater. It can change flow magnitude and regime along a river, particularly for Transboundary Rivers shared by multiple jurisdictions. This study develops a coupled framework to assess both the current and future cumulative impacts of damming on downstream water availability for data-sparse regions like the Tibetan Plateau. The framework is applied to the Brahmaputra River Basin (BRB), where dam developments on the Tibetan Plateau are highly concerned. The results show that, despite being part of the ‘Asian water tower’, the Yarlung Tsangpo River (YTR) contributes just 15–16% to Brahmaputra streamflow, for 48% of its contributing area. We found that the maximum impact due to five recently constructed dams in YTR suggests about 8–11% reduction of mean annual streamflow at outlet of Brahmaputra River. The impacts of damming would be largely offset by runoff increases under the climate scenarios projected by 28 CMIP5 model outputs from RCP4.5 median-level emission scenarios and 29 CMIP5 model outputs from RCP8.5 high-level emission scenarios for the period of 2049 to 2075, compared to the historical period of 1979 to 2005. Our results suggest that it is necessary to use our framework or a similar one to comprehensively evaluate the maximum possible damming impact across the Transboundary Rivers.