Scale-dependent parameter models were developed and nested to the Soil and Water Assessment Tool-SWAT to simulate climate and land use change impacts on water-sediment-nutrient yields in Benin at a regional scale (49,256 km²). Weighted contributions of relevant landscape attributes characterizing the spatial pattern of ongoing hydrological processes were used to constrain the model parameters to acceptable physical meanings. Climate change projections (describing a rainfall reduction of up to 25%) simulated throughout the Regional Model-REMO, very sensitive to a prescribed degradation of land cover, were considered. Land use change scenarios in which the population growth was translated into a specific demand for settlements and croplands (cropland increase of up to 40%) according to the development of the national framework, were also considered. The results were consistent with simulations performed at the meso-scale (586 km2) where local management operations were incorporated. Surface runoff, groundwater flow, sediment and organic N and P yields were affected by land use change (as major effects) of −8% to +50%, while water yield and evapotranspiration were dominantly affected by climate change of −31% to +2%. This tendency was more marked at the regional scale as response to higher scale-dependent rates of natural vegetations with higher conversions to croplands.