This study presents an analysis of the impacts of climate change on thermal comfort and energy performance of residential buildings in Ghana, in sub-Saharan Africa, and explores mitigation as well as adaptation strategies to improve buildings' performance under climate change conditions. The performances of the buildings are analyzed for both recent and projected future climates for the Greater Accra and Ashanti regions of Ghana, using the IDA-ICE dynamic simulation software, with climate data from the Meteonorm global climate database. The results suggest that climate change will significantly influence energy performance and indoor comfort conditions of buildings in Ghana. However, effective building design strategies could significantly improve buildings' energy and indoor climate performances under both current and future climate conditions. The simulations show that the cooling energy demand of the analyzed building in the Greater Accra region is 113.9 kWh/m(2) for the recent climate, and this increases by 31% and 50% for the projected climates for 2030 and 2050, respectively. For the analyzed building in the Ashanti region, the cooling energy demand is 104.4 kWh/m(2) for the recent climate, and this increases by 6% and 15% for the 2030 and 2050 climates, respectively. Furthermore, indoor climate and comfort deteriorate under the climate change conditions, in contrast to the recent conditions.