The urbanization process has significantly impacted urban morphology, which in turn has led to changes in the urban surface thermal environment (USTE). A summarization of the empirical patterns of past urban morphology changes and an evaluation of the USTE effects produced by different patterns will contribute to the advancement of scientific knowledge regarding the response of USTE to urban morphology changes and facilitate the development of sustainable urban planning and design practices. This study investigated the response of USTE to urban morphology from the overall and local based on the Local Climate Zone (LCZ) framework during 2005–2020 in Nanjing. The results validated the rationality of the LCZ framework for describing urban morphology changes and their USTE responses. It was found that the overall USTE was continuing to deteriorate, with an increase in high temperature and sub-high temperature areas. LCZ 4, LCZ 5, and LCZ 8 were the major contributors to overall urban heat, and their growth in the amount and changes in USTE characteristics mainly caused the overall USTE deterioration. In localized areas, it was found that urban regeneration had the most potential to optimize USTE. The conversion processes of LCZ 5 to LCZ 4, LCZ 8 to LCZ 4, and LCZ 8 to LCZ 5 were considered more advantageous in improving daytime USTE, which should be advocated. The results can provide important insights into the perception of urban morphology and USTE, and support the urban regeneration policies for climate-resilient cities from the environmental performance perspective.