<p>The impact of climate and land use changes is increasingly threatening the sustainability of the major river basins in Madagascar (MRBM). We assess the potential impacts of climate and land cover change on future water availability across the MRBM for the period 2040–2080, and develop an efficient resource assessment method for data-scarce basins at the national level. The Inter-Sectoral Impact Model Intercomparison Project (ISIMIP3b) is used as a framework to compare Soil and Water Assessment Tool (SWAT model) performances for future climate change and socio-economic conditions. The results are compared with those of a previous study on Inter- and Intra-basin approaches using a Bland–Altman plot and linear regression analysis. ISIMIP3b shows that an ensemble of 10 bias-corrected global circulation models efficiently simulated the future impacts of climate change across the MRBM. Overall, climate change is predicted to decrease precipitation and increase maximum and minimum temperatures across the MRBM under Shared Socioeconomic Pathways 3 and 5 by 2080. Different combinations of climate and land cover changes will significantly impact future water availability, leading to significant seasonal shifts. Importantly, our analysis reveals reasonable agreement between the Inter- and Intra-basin approaches and the SWAT model in quantifying potential water resources per capita and agriculture areas under both historical and future scenarios. We recommend the Inter- and Intra-basin methods for assessing water resources in data-scarce basins, as they rely on a simple long-term water balance method and require fewer input data than the SWAT model.</p>