We used the General Ensemble biogeochemical Modeling System (GEMS) to simulate responses of natural and managed ecosystems to changes in land use and land cover, management, and climate for a forest/savanna transitional zone in central Ghana. Model results show that deforestation for crop production during the 20th century resulted in a substantial reduction in ecosystem carbon (C) stock from 135.4 Mg C ha⁻¹ in 1900 to 77.0 Mg C ha⁻¹ in 2000, and in soil organic C stock within the top 20 cm of soil from 26.6 Mg C ha⁻¹ to 21.2 Mg C ha⁻¹. If no land use change takes place from 2000 through 2100, low and high climate change scenarios (increase in temperature and decrease in precipitation over time) will result in losses of soil organic C stock by 16% and 20%, respectively. A low nitrogen (N) fertilization rate is the principal constraint on current crop production. An increase in N fertilization under the low climate change scenario would lead to an increase in the average crop yield by 21% with 30 kg N ha⁻¹ and by 42% with 60 kg N ha⁻¹ (varying with crop species), accordingly, the average soil C stock would decrease by 2% and increase by 17%, in all cropping systems by 2100. The results suggest that a reasonable N fertilization rate is critical to achieve food security and agricultural sustainability in the study area through the 21st century. Adaptation strategies for climate change in this study area require national plans to support policies and practices that provide adequate N fertilizers to sustain soil C and crop yields and to consider high temperature tolerant crop species if these temperature projections are exceeded.