The bio-geophysical effects of land cover classes are considered to be an important factor in land surface temperature variations between urban and suburban areas. This means that major cities are significantly warmer than surrounding suburban or rural areas, which is known as the Urban Heat Island (UHI) effect. The aim of this study was to assess and analyze the spatiotemporal variation, correlation and impact of UHIs on Mekelle city (1990–2020) using remote sensing techniques. The study's primary objective was accomplished using the a number of techniques, including the extraction of LULC classes, estimation of the seasonal LSTs, assessment of UHI and UTFVI, and showing the relationship between LULC and LST as well as the interactions between UHI, UTFVI, and urban LULC classes. By analyzing TIRs/OLI thermal band data after calibrating uncertainty in the images and validating it using the concept of theoretical relationships and least squares fitting method, estimates of local LST, UHI (both in Mekelle and periphery rural areas), and UTFVI were obtained. The result of standard multiple regression models showed that impervious urban land surface, built-up areas, and dry bare soil highly contribute and influence variation at LST intensity caused for the formation of UHI in the study area. The result showed that the maximum UHI value in Mekelle city was 2.73 °C during the dry season in 1990. It decreased slightly to 2.53 °C in 2000 and then increased regularly to 2.83 °C and 2.98 °C in 2010 and 2020, respectively. To determine the city's UHI status in comparison to eight selected peripheral suburban areas, a trend analysis has been done. The UHI intensity of Mekelle city was higher relatively to that of most of the periphery suburban districts, particularly in 2020 (both dry and rainy seasons); this could be due to the city's explosive growth. It's worth noting that the research area affected by the urban heat island effect has grown over time, and as a result, the study area also has severe microclimate conditions that primarily damage the quality of urban life and create the worst conditions for thermal discomfort. The results of this study provide major conceptual understandings of how improper distribution and use of urban land affects the urban environment and fuels the creation of the UHI and thermal discomfort phenomena. Hence policy makers and urban planners should consider the effects of LST and UHI and integrate UHI comprehensive mitigation strategies with urban development patterns, and current and projected local climate changes in order to create sustainable urban environments, cities, and communities. In conclusion, compared to the conventional method, satellite remote sensing provides a faster and more efficient method for researching LST and UHI.