The urban heat island (UHI) is mostly due to urbanization. This phenomenon in concert with the high temperatures caused by global climate change may profoundly affect human thermal comfort, which can influence human productivity and morbidity especially in spring/summer period. The main objective of this investigation was to determine changes in degree of thermal comfort of Mexico City’s inhabitants and compare it with the physiological equivalent temperature (PET) to evaluate whether PET and its categorization are adequate to be applied in Mexico City. A series of microclimatological measurements to estimate PET were made in four sites including the city´s center. Concomitantly, a series of surveys of thermal perception were applied to 1300 passersby. The results show that PET has increased from 1990 to 2020 from 0.1208 °C/year to 0.1498 °C/year in the study sites, besides overestimating the degree of thermal comfort of people according to the stablished categories or classes. It is concluded that it is necessary to adjust thermal stress categories. Knowing the percentage of people without thermal comfort will lead us to determine different ranges in environmental parameters to define an acceptable environment for most people.