Hydrological processes and the sustainable use of water resources in a river basin are altered by climate change and changes in human variables. This study examined the significant effects of vegetation and hydrological, climatic, and human activity changes on the basin’s biological environment and usage of water resources. The Min River Basin (MRB) in the upper Yangtze River served as the study location. Mann–Kendall and Pettitt mutation test techniques were used to examine the features of runoff changes in the basin. The effects of meteorological and anthropogenic factors on runoff and vegetation changes in the MRB from 1982 to 2020 were quantitatively evaluated using the expanded Budyko equation. Following this, spatial and temporal variations in land use and the NDVI in the basin were studied. The results of the research demonstrated the following: (1) The MRB yearly runoff trended downward and that an abrupt change in runoff happened in 1994. (2) Precipitation (Pr) showed a decreasing tendency from the base period (S1) to the change period (S2), but potential evapotranspiration (ET0) showed an increasing trend. (3) From 1985 to 2020, the land use area of the MRB changed rapidly, and the construction land and water area increased by 322% and 58.85%, respectively, while the cultivated land area decreased by 11.72%. (4) From S1 to S2, there was a rising trend in both the NDVI and the Budyko parameter n. The contributions of Pr, ET0, NDVI, and n to the runoff change were 32.41%, 9.43%, 27.51%, and 30.65%, respectively.