Exposure to heat and heatwaves are associated with mortality and may amplify morbidities. In a climate change context, projections suggest temperatures will likely rise in the foreseeable future. Our paper assesses the current knowledge on human health effects of heat exposure and gathered local knowledge of heat-health effects in a rural area of the Agincourt sub-district of South Africa. Existing, peer-reviewed published literature on heat effects on human health as well as heat-health indicators was reviewed. Interviews and structured observations to collect data on heat effects on human health in Agincourt sub-district were conducted. The Lancet Countdown heat-related indicators were applied as a framework against which to discuss our findings. A total of 93 participants who lived in Agincourt sub-district for 5 years and more were interviewed. Participants reported that temperatures, especially summertime temperatures, had been rising over the past years. Health effects of heat were deemed more apparent in relation to morbidity. Heatwaves were not easily comprehensible as singular ‘events’, and their effects were poorly understood. The population groups disproportionately affected by heat included infants, the elderly, those living with disability and outdoor workers. High ambient temperatures were deemed to be associated with reduced labour productivity of outdoor workers. Community-level perceptions of heat impacts on health were mainly related to illnesses and diseases, with no understanding of mortality risk. Future health awareness campaigns that encompass the full range of heat-health impacts are essential to reduce vulnerability, morbidity, and mortality. Our study provided location-specific, qualitative, and indicator-aligned data for a geographic area expected to undergo significant heat stress in the future. The study findings have significant research, policy, and practice implications in similar resource-limited settings.