Aggregated mining development has direct and indirect impacts on vegetation changes. This impact shows spatial differences due to the complex influence of multiple mines, which is a common issue in resource regions. To estimate the spatial heterogeneity of vegetation response to mining activities, we coupled vegetation changes and mining development through a geographically weighted regression (GWR) model for three cumulative periods between 1999 and 2018 in integrated resource regions of northwestern China. Vegetation changes were monitored by Sen’s slope and the Mann–Kendall test according to a total of 72 Landsat images. Spatial distribution of mining development was quantified, due to four land-use maps in 2000, 2005, 2010, and 2017. The results showed that 80% of vegetation in the study area experienced different degrees of degradation, more serious in the overlapping areas of multiple mines and mining areas. The scope of influence for single mines on vegetation shrunk by about 48%, and the mean coefficients increased by 20%, closer to mining areas. The scope of influence for multiple mines on vegetation gradually expanded to 86% from the outer edge to the inner overlapping areas of mining areas, where the mean coefficients increased by 92%. The correlation between elevation and vegetation changes varied according to the average elevation of the total mining areas. Ultimately, the available ecological remediation should be systematically considered for local conditions and mining consequences.