Agricultural land use alters regional climate through modifying the surface mass, energy, and momentum fluxes; climate influences agricultural land use through their impact on crop yields. These interactions are not well understood and have not been adequately considered in climate projections. This study tackles the critical linkages within the coupled natural-human system of West Africa in a changing climate based on an equilibrium application of a modeling framework that asynchronously couples models of regional climate, crop yield, multimarket agricultural economics, and cropland expansion. Using this regional modeling framework driven with two global climate models, we assess the contributions of land use change (LUC) and greenhouse gas (GHGs) concentration changes to regional climate changes and assess the contribution of climate change and socioeconomic factors to agricultural land use changes. For future cropland expansion in West Africa, our results suggest that socioeconomic development would be the dominant driver in the east (where current cropland coverage is already high) and climate changes would be the primary driver in the west (where future yield drop is severe). For future climate, it is found that agricultural expansion would cause a dry signal in the west and a wet signal in the east downwind, with an east-west contrast similar to the GHG-induced changes. Over a substantial portion of West Africa, the strength of the LUC-induced climate signals is comparable to the GHG-induced changes. Uncertainties originating from the driving global models are small; human decision making related to land use and international trade is a major source of uncertainty.