The variation of land surface temperature (LST) has a vital impact on the energy balance of the land surface process and the ecosystem stability. Based on MDO11C3, we mainly used regression analysis, GIS spatial analysis, correlation analysis, and center-of -gravity model, to analyze the LST variation and its spatiotemporal differentiation in China from 2001 to 2020. Furthermore, we employed the Geodetector to identify the dominant factors contributing to LST variation in 38 eco-geographic zones of China and investigate the underlying causes of its pattern. The results indicate the following: (1) From 2001 to 2020, the LST climate average in China is 9.6℃, with a general pattern of higher temperatures in the southeast and northwest regions, lower temperatures in the northeast and Qinghai-Tibet Plateau, and higher temperatures in plains compared to lower temperatures in mountainous areas. Generally, LST has a significant negative correlation with elevation, with a correlation coefficient of -0.66. China’s First Ladder has the most pronounced negative correlation, with a correlation coefficient of -0.76 and the lapse rate of LST is 0.57℃/100 m. (2) The change rate of LST in China during the study is 0.21℃/10 a, and the warming area accounts for 78%, demonstrating the overall spatial pattern a “multi-core warming and axial cooling”. (3) LST’s variation exhibits prominent seasonal characteristics in the whole country. The spatial distribution of average value in winter and summer differs significantly from other seasons and shows more noticeable fluctuations. The centroid trajectory of the seasonal warming/cooling area is close to a loop shape and displays corresponding seasonal reverse movement. Cooling areas exhibit more substantial centroid movement, indicating greater regional variation and seasonal variability. (4) China’s LST variation is driven by both natural influences and human activities, of which natural factors contribute more, with sunshine duration and altitude being key factors. The boundary trend between the two dominant type areas is highly consistent with the “Heihe-Tengchong Line”. The eastern region is mostly dominated by human activity in conjunction with terrain factors, while the western region is predominantly influenced by natural factors, which enhance/weaken the change range of LST through mutual coupling with climate, terrain, vegetation, and other factors. This study offers valuable scientific references for addressing climate change, analyzing surface environmental patterns, and protecting the ecological environment.