The rising global temperatures have posed challenges to human survival and well-being in various regions worldwide. However, little is known about human thermal stress exposure changes among populations living in extreme poverty and struggling to meet their basic needs. This study aimed to investigate the spatial patterns of changes in human thermal stress levels in South Asia using the Universal Thermal Climate Index (UTCI). ERA5 HEAT data from 1979 to 2021 were analyzed using Sen's slope method and the Modified Mann-Kendall test to determine the changes in annual and seasonal thermal stress levels. The findings revealed that Bangladesh, located in the eastern part of South Asia, experiences the highest mean UTCI range (26 to 32 °C), while Afghanistan has the lowest among the South Asian nations. In contrast, the western part of South Asia, particularly the region bordering India and Pakistan, exhibits the highest daily maximum UTCI range (38 to 46 °C). Trend analysis indicated an increase in mean and maximum UTCI levels across the western part of South Asia, including Pakistan, Afghanistan, and northwest India, at 0.25 to 0.75 °C/decade. This increase was more widespread during the June–September (JAS) period than in other seasons. In many regions of the study area, moderate and high thermal stress days increased by 4 to 8 days per decade. As a result, 27.6% of the area shifted from an average comfortable temperature to moderate thermal stress and 18.7% from moderate to strong thermal stress during JAS.