Tropical terrestrial ecosystems across African continent play an increasing role in the global carbon cycle with potentially significant climate change implications. We used the General Ensemble biogeochemical Modeling System (GEMS) to simulate responses of natural and managed systems to changes in land use, management, and climate for the transitional zone of forest and savanna across the Ejura district of Ghana. Model inputs included time-series land use/land cover images, historical climate records, soil characterization, and management inventory. Our results show that the conversion of natural open forest and closed dense savanna to agricultural use resulted in a substantial reduction in ecosystem and soil carbon stocks. In addition to the dramatic reduction associated with changes in land use, the dynamics of soil organic carbon depend on land management practices and climate variables. Low nitrogenous fertilizer level is the principal constraint on current crop production and presents a progressive threat to food security under the changing climate. An increase in nitrogen fertilization would be a critical measure to achieve food security and agricultural sustainability in the 21st century.