Analysis of land surface temperature (LST) spatiotemporal variations and characterization of the factors affecting these variations are of great importance in various environmental studies and applications. The aim of this study is to propose an integrated model for characterizing LST spatiotemporal variations and for assessing the impact of surface biophysical parameters on the LST variations. For this purpose, a case study was conducted in Babol City, Iran, during the period of 1985 to 2018. We used 122 images of Landsat 5, 7, and 8, and products of water vapor (MOD07) and daily LST (MOD11A1) from the MODIS sensor of the Terra satellite, as well as soil and air temperature and relative humidity data measured at the local meteorological station over 112 dates for the study. First, a single-channel algorithm was applied to estimate LST, while various spectral indices were computed to represent surface biophysical parameters, which included the normalized difference vegetation index (NDVI), soil-adjusted vegetation index (SAVI), normalized difference water index (NDWI), normalized difference built-up index (NDBI), albedo, brightness, greenness, and wetness from tasseled cap transformation. Next, a principal component analysis (PCA) was conducted to determine the degree of LST variation and the surface biophysical parameters in the temporal dimension at the pixel scale based on Landsat imagery. Finally, the relationship between the first component of the PCA of LST and each surface biophysical parameter was investigated by using the ordinary least squares (OLS) regression with both regional and local optimizations. The results indicated that among the surface biophysical parameters, variations of NDBI, wetness, and greenness had the highest impact on the LST variations with a correlation coefficient of 0.75, −0.70, and −0.44, and RMSE of 0.71, 1.03, and 1.06, respectively. The impact of NDBI, wetness, and greenness varied geographically, but their variations accounted for 43%, 38%, and 19% of the LST variation, respectively. Furthermore, the correlation coefficient and RMSE between the observed LST variation and modeled LST variation, based on the most influential biophysical factors (NDBI, wetness, and greenness) yielded 0.85 and 1.06 for the regional approach and 0.93 and 0.26 for the local approach, respectively. The results of this study indicated the use of an integrated PCA–OLS model was effective for modeling of various environmental parameters and their relationship with LST. In addition, the PCA–OLS with the local optimization was found to be more efficient than the one with the regional optimization.