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The long-term impact of rapid urbanization on air temperature (T-a), relative humidity (RH), vapor pressure (VP) and human thermal comfort in the Cairo governorate of Egypt was analyzed. Land use change (LUC) between 1973 and 2017 were derived from Landsat satellite data. Next, non-parametric change point and trend detection algorithms were applied to T-a, RH and VP over 1950-2017 to estimate the impacts of urbanization on urban climate. Three historical thermal comfort indices: temperature humidity index (THI), effective temperature index (ETI) and relative strain index (RSI) were estimated from climate data collected between 1950 and 2017 to assess the impact of urbanization on human thermal comfort. The results reveal substantial LUC, rapid increasing impervious surface areas in low-lying areas of Cairo at 75.2 km(2)/decade since the 1990s. Rapid urbanization had resulted in a statistically significant change point in T-a after 1995 with a warming trend of 0.19 degrees C/decade, a negative trend in RH of 0.55%/decade and a rising trend in VP of 0.24 hPa/decade. Severe heat stress levels emerged and persisted every July September since 1994. THI, ETI, and RSI show statistically significant change points at 1994 and a rising trend of 0.33 degrees C/decade, 0.29 degrees C/decade, and 0.06/decade, respectively. The highest thermal discomfort risk was found in urban areas of the old Cairo, but the risk is marginally smaller at new cities where there are vegetation covers. This study clearly demonstrates the impacts of rapid urbanization on the urban climate of hot-arid environment.