The Black Volta River basin faces several challenges, which impede the sustainability of its water resources and biodiversity. Climate change coupled with land use/land cover (LULC) change patterns account for most of the observed hydrological changes in the basin. The aim of this study was to assess the impact of changes in the climate and LULC on water resources in the basin, and its effect on the livelihoods of downstream users, particularly regarding water allocations. The water evaluation and planning (WEAP) model was applied to the assessment of runoff and streamflow and the percentage future water demand under climate change scenarios (RCP 2.6 and RCP 8.5), as well as the effects of current and future changes on water supply systems. LULC data from 1990 to 2019 were processed to detect the changes in LULC patterns in the basin. The results showed that from 1990 and 2019, the land use classes of settlements/bare ground, open savannah woodland, croplands, and waterbodies increased by 339.5%, 77.4%, 24.4%, and 607%, respectively. Close savannah woodlands, wetlands, and grasslands all decreased by 97%, 99.8%, and 21.2%, respectively. Overall, there was a significant difference in LULC changes. Hence, measures needed to be put in place to curb the changes, as the observed changes posed a serious challenge to the basin’s water resources. The results from the WEAP simulations also indicated that in the future, changes in discharge would be visible in September with ranges between 0.72 × 106 m3 and 1.9 × 106 m3 for RCP 2.6, and 0.65 × 106 m3 and 2.5 × 106 m3 for RCP 8.5, per month. Although the median values illustrate an increase in water availability from river discharge compared with the reference scenario, the uncertainties in future changes largely exceeded the predicted increases. Annual variability of the mean annual flows is projected to decrease over the period in the Black Volta Basin. Therefore, the outcomes of this study will be useful for different stakeholders within the basin in water resources planning and the formulation of appropriate policies for improving land use planning.