Due to the potential impact of climate change and climate variability on rainfed production systems, both farmers and policy makers will have to rely more on short- and long-term yield projections. The goal of this study was to develop a procedure for calibrating the Cropping System Model (CSM)-CROPGRO-Soybean model for six cultivars, to determine the potential impact of climate change on rainfed soybean for five locations in Georgia, USA, and to provide recommendations for potential adaptation strategies for soybean production in Georgia and other south-eastern states. The Genotype Coefficient Calculator (GENCALC) software package was applied for calibration of the soybean cultivar coefficients using variety trial data. The root mean square error (RMSE) between observed and simulated grain yield ranged from 201 to 413 kg/ha for the six cultivars. Generally, the future climate scenarios showed an increase in temperature which caused a decrease in the number of days to maturity for all varieties and for all locations. This will benefit late-planted soybean production slightly, while the increase in precipitation and carbon dioxide (CO2) concentration will result in a yield increase. This was the highest for Calhoun and Williamson and ranged from 31 to 49% for the climate change projections for 2050. However, a large reduction in precipitation caused a decrease in yield for Midville, especially based on the climate scenarios of the Global Climate Models (GCMs) Commonwealth Scientific and Industrial Research Organisation's model CSIRO-Mk3.0 and Geophysical Fluid Dynamics Laboratory's model GFDL-CM2.1. Overall, Calhoun, Williamson, Plains and Tifton will probably be more suitable for rainfed soybean production over the next 40 years than Midville. Farmers might shift to a later planting date, around 5 June, for the locations that were evaluated in the present study to avoid potential heat and drought stress during the summer months. The cultivars AG6702, AGS758RR and S80-P2 could be selected for rainfed soybean production since they had the highest rainfed yields among the six cultivars. In general, the present study showed that there are crop management options for soybean production in Georgia and the south-eastern USA that are adapted for the potential projected climate change conditions.