As the scientific consensus concerning global climate change has increased in recent decades, research on potential impacts of climate change on water resources has been given high importance. However in Sub-Saharan Africa, few studies have fully evaluated the potential implications of climate change to their water resource systems. The Volta River is one of the major rivers in Africa covering six riparian countries (mainly Ghana and Burkina Faso). It is a principal water source for approximately 24 million people in the region. The catchment is primarily agricultural providing food supplies to rural areas, demonstrating the classic water, food, energy nexus. In this study an Integrated Catchment Model (INCA) was applied to the whole Volta River system to simulate flow in the rivers and at the outlet of the artificial Lake Volta. High-resolution climate scenarios downscaled from three different Global Climate Models (CNRM-CM5, HadGEM2-ES and CanESM2), have been used to drive the INCA model and to assess changes in flow by 2050s and 2090s under the high climate forcing scenario RCP8.5. Results show that peak flows during the monsoon months could increase into the future. The duration of high flow could become longer compared to the recent condition. In addition, we considered three different socio-economic scenarios. As an example, under the combined impact from climate change from downscaling CNRM-CM5 and medium+ (high economic growth) socio-economic changes, the extreme high flows (Q5) of the Black Volta River are projected to increase 11% and 36% at 2050s and 2090s, respectively. Lake Volta outflow would increase +1% and +5% at 2050s and 2090s, respectively, under the same scenario. The effects of changing socio-economic conditions on flow are minor compared to the climate change impact. These results will provide valuable information assisting future water resource development and adaptive strategies in the Volta Basin.