This study explores how a vegetation cover (VC) index can be employed as a pollution warning tool in gold mining areas in the Northwest of Iran. The analysis included the following: (a) the extraction of normalized difference vegetation index (NDVI) maps from Landsat images in three zones, i.e., mining operations, upstream areas without any exploration, and the downstream area of the mining activities, (b) calculation of the zones' VC, (c) investigation of transformation trends in each pixel of VC time series using the Mann-Kendall trend test, (d) determination of the pixels with significant VC reduction and the significant starting points of the trend using the sequential Mann-Kendall test, (e) assessment of the correlation between the zones with significantly reduced VC, and (f) a correlation test between average monthly and annual climate parameters and VC. Our results indicate that although 51 ha of VC has been demolished around the mining activities areas (i.e., zone 1), an overall upward trend in vegetation with no chemical leakage is observed into the downstream area of the basin (i.e., zone 3). This upward trend can be mostly attributed to the increasing precipitation and decreasing temperature in the study period. The fact that the area downstream of the mine shows that the heap leaching method for gold mining in Andaryan mine is currently not damaging the vegetation, this likely means that there is no leakage to the surrounding environment from the mine. Our results further show that using NDVI in a pixel-based scale and statistical methods has a high potential to quantify the effects of human activities on surface biophysical characteristics.