Agriculture in West Africa is constrained by several yield-limiting factors, such as poor soil fertility, erratic rainfall distributions and low input systems. Projected changes in climate, thus, pose a threat since crop production is mainly rain-fed. The impact of climate change and its variation on the productivity of cereals in smallholder settings under future production systems in Navrongo, Ghana and Nioro du Rip, Senegal was assessed in this study. Data on management practices obtained from household surveys and projected agricultural development pathways (through stakeholder engagements), soil data, weather data (historical: 1980–2009 and five General Circulation Models; mid-century time slice 2040–2069 for two Representative Concentration Pathways; 4.5 and 8.5) were used for the impact assessment, employing a crop simulation model. Ensemble maize yield changes under the sustainable agricultural development pathway (SDP) were −13 and −16%, while under the unsustainable development pathway (USDP), yield changes were −19 and −20% in Navrongo and Nioro du Rip, respectively. The impact on sorghum and millet were lower than that on maize. Variations in climate change impact among smallholders were high with relative standard deviations (RSD) of between 14% and 60% across the cereals with variability being higher under the USDP, except for millet. Agricultural production systems with higher intensification but with less emphasis on soil conservation (USDP) will be more negatively impacted by climate change compared to relatively sustainable ones (SDP).