Urbanization combined with global climate change, exacerbates the urban thermal environment and hinders sustainable urban development. However, the complex relationships between land surface temperature (LST) and urban morphology are being further understood, particularly in relation to different urban development patterns, distinct topography, and 3D building morphology. Thus, this study conducted a comparative study in Chengdu and Chongqing, Southwest China. We explored the impact of comprehensive factors (including socio-economic factos, topography, land use composition, and building morphology) on LST by employing the methods of linear regression, geographical detector model, and the boosted regression trees. Our results suggest that (1) high LST was mainly observed in the central part of Chengdu but it presented multicenter aggregation trend in Chongqing; (2) Socio-economic factors were the dominant variables affecting LST in both cities; (3) land use composition and building morphology showed distinct contributions to LST among the two cities; and (4) 3D building management was more effective in Chengdu than in Chongqing. A better understanding of the impact of various influencing factors on LST will enable policy makers and planners to develop appropriate strategies for constructing climate-adaptive cities and mitigating urban heat.