The production of soybean is gaining more attention in West Africa. In light of projected changes in climate, there is a need to assess the potential impacts on yield productivity and variability among farmers. An evaluated GROPGRO module of the Decision Support System for Agro-technological Transfer (DSSAT) was used to simulate soybean productivity under both historical (1980–2009) and projected climate scenarios from multiple general circulation models (GCMs) under two representative concentration pathways (RCPs): 4.5 and 8.5. Agronomic data from 90 farms, as well as multiple soil profile data, were also used for the impact assessment. Climate change leads to a reduction (3% to 13.5% across GCMs and RCPs) in the productivity of soybean in Northern Ghana. However, elevated atmospheric carbon dioxide has the potential to offset the negative impact, resulting in increased (14.8% to 31.3% across GCMs and RCPs) productivity. The impact of climate change on yield varied widely amongst farms (with relative standard deviation (RSD) ranging between 17% and 35%) and across years (RSD of between 10% and 15%). Diversity in management practices, as well as differences in soils, explained the heterogeneity in impact among farms. Variability among farms was higher than that among years. The strategic management of cultural practices provides an option to enhance the resilience of soybean productivity among smallholders.