Agriculture is the mainstay of Malawi’s economy and maize is the most important crop for food security. As a Least Developed Country (LDC), adverse effects of climate change (CC) on agriculture in Malawi are expected to be significant. We examined the impacts of CC on maize production and food security in Malawi’s dominant cereal producing region, Lilongwe District. We used five Global Circulation Models (GCMs) to make future (2011 to 2100) rainfall and temperature projections and simulated maize yields under these projections. Our future rainfall projections did not reveal a strong increasing or decreasing trend, but temperatures are expected to increase. Our crop modelling results, for the short-term future, suggest that maize farming might benefit from CC. However, faster crop growth could worsen Malawi’s soil fertility problem. Increasing temperature could drive lower maize yields in the medium to long-term future. Consequently, up to 12% of the population in Lilongwe District might be vulnerable to food insecurity by the end of the century. Measures to increase soil fertility and moisture must be developed to build resilience into Malawi’s agriculture sector.