In 2015, with the signing of the “Paris Agreement”, 195 countries committed to limiting the increase in global temperature to less than 2 °C with respect to pre-industrial levels and to aim at limiting the increase to 1.5 °C by 2100. The regional ramifications of those thresholds remain however largely unknown and variability in the magnitude of change and the associated impacts are yet to be quantified. We provide a regional quantitative assessment of the impacts of a 1.5 versus a 2 °C global warming for a major global climate change hotspot: the Indus, Ganges, and Brahmaputra river basins (IGB) in South Asia, by analyzing changes in climate change indicators based on 1.5 and 2 °C global warming scenarios. In the analyzed ensemble of general circulation models, a global temperature increase of 1.5 °C implies a temperature increase of 1.4–2.6 (μ = 2.1) °C for the IGB. For the 2.0 °C scenario, the increase would be 2.0–3.4 (μ = 2.7) °C. We show that climate change impacts are more adverse under 2 °C versus 1.5 °C warming and that changes in the indicators’ values are in general linearly correlated to average temperature increase. We also show that for climate projections following Representative Concentration Pathways 4.5 and 8.5, which may be more realistic, the regional temperature increases and changes in climate change indicators are much stronger than for the 1.5 and 2 °C scenarios.