Vulnerability to climate change is a complex and dynamic phenomenon involving both social and physical/environmental aspects. It is presented as a method for the quantification of the vulnerability of all municipalities of Minas Gerais, a state in southeastern Brazil. It is based on the aggregation of different kinds of environmental, climatic, social, institutional, and epidemiological variables, to form a composite index. This was named “Index of Human Vulnerability” and was calculated using a software (SisVuClima®) specifically developed for this purpose. Social, environmental, and health data were combined with the climatic scenarios RCP 4.5 and 8.5, downscaled from ETA-HadGEM2-ES for each municipality. The Index of Human Vulnerability associated with the RCP 8.5 has shown a higher vulnerability for municipalities in the southern and eastern parts of the state of Minas Gerais.