Land cover change (LCC) and climate change (CC) impacts on streamflow in high elevated catchments are a great challenge to sustainable management and the development of water resources. This study evaluates the possible future impacts of both land cover and climate change on the streamflows in the Mohmand Dam catchment, Pakistan, by utilizing the semi-distributed hydrological model known as the Soil and Water Assessment Tool (SWAT), along with the latest Coupled Model Intercomparison Project phase 6 (CMIP6) dataset of different global climate models (GCMs). The downscaling of the precipitation and temperature data was performed by the CMhyd software. The downscaled precipitation and temperature projections from the best performing GCM, out of four GCMs, under two shared socioeconomic pathways (SSP2 and SSP5) and future land cover conditions were forced in a calibrated hydrological model (SWAT model). Compared to the baseline period (1990–2015), the outputs from the selected GCM indicated an increase in the average monthly precipitation, and the maximum and minimum temperature in the study area under both the SSP2 and SSP5 scenarios, by the end of the 21st century. It is expected that the increase in precipitation for the period 2016–2100 is 10.5% and 11.4% under the SSP2 and SSP5 scenarios, respectively. Simulated results from the SWAT model showed significant impacts from the projected climate and land cover changes on Mohmand Dam flows that include: (a) an increase in the overall mean annual flow ranging from 13.7% to 34.8%, whereas the mean monthly flows of June, July and August decreased, and (b) a shift in the peak flows in the Mohmand catchment from July to June. It is concluded that the projected climate changes can substantially influence the seasonality of flows at the Mohmand Dam site. Climate and land cover change impacts are significant, so project planners and managers must include CC and LCC impacts in the proposed operational strategy.