This study analysed the separate and the combined impacts of climate and land use changes on hydrology on the Bonsa catchment in Ghana, West Africa, using the ACRU hydrological model. The study used five RCP8.5 climate change scenarios (wet, 25th percentile, 75th percentile, dry and a multi-model median of nine GCMs) from the CMIP5 AR5 models for near (2020–2039) and far (2060–2079) future time slices. Change factors were used to downscale the GCM scenarios to the local scale, using observed climate data for the control period of 1990 to 2009. The land use of 1991 and 2011 were used as the baseline and current land use as well as three future land use scenarios (BAU, EG, EGR) for two time slices (2030 and 2070) were used. The study showed that under all separate climate change scenarios, overall flows reduced, but under combined climate and land use changes, streamflows increased. Under the combined scenarios, streamflow responses due to the different future land use scenarios were not substantially different. Also, land use is the dominant controlling factor in streamflow changes in the Bonsa catchment under a dry climate change, but under a wet climate change, climate controls streamflow changes. The spatial variability of catchment streamflow changes under combined land use and climate changes were greater than the spatial variability of streamflow changes under climate change. The range of plausible future streamflows changes derived in this study provides natural resources and environmental managers of the Bonsa catchment, the first ever and the most current information to develop suitable adaptation and mitigation strategies, to prepare adequately for climate and land use changes.