Global climate models predict increases in the frequency and intensity of extreme heat events across the African continent during the remainder of the twenty-first century. Projected increases in temperature extremes have significant implications for humanity, particularly in the African Great Lakes region (GLR) where some of the world's poorest and most vulnerable populations reside. Using high-resolution Community Earth System Model (CESM) simulations to investigate the impacts of climate change under Representative Concentration Pathway (RCP) 8.5 and spatially explicit population trajectories consistent with two shared socio-economic pathways (SSPs), we contrast early and projected late century human exposure to temperature extremes and the associated potential health impacts for nine countries of the GLR. While all countries are projected to experience increases in the number of heat stress days, the greatest increases occur in the north and west, in parts of Kenya, Uganda, and the Democratic Republic of Congo. Nighttime relief diminishes due to 3-8A degrees increases in average minimum temperatures. Country-wide population exposure to extreme heat stress increases 7- to 269-fold over current levels. Total population growth as well as rural-urban distribution patterns strongly influence outcomes, but to a lesser degree than the warming climate.