The intensification of anthropic uses (i.e., increase of the hemerobic condition) threatens the remnants of native vegetation due to the reduction of its self-regulation capacity. In this research, the Distance to Nature (D2N) index for land use and land cover was applied in the Río Grande de Comitán watershed (Southern Mexico) to answer the following questions: 1) What were the land use dynamics observed in the Rio Grande de Comitán watershed in the trajectory through 1999, 2009 and 2019? 2) Does the subcategorization of the D2N allow one to identify which anthropic uses influence more the territorial expression of the watershed? To answer these questions, we performed a supervised classification of land use and land cover was performed in this watershed, and for the D2N index, the classification was simplified to threecategory scale for the subcategorization of the anthropic component. Through Principal Component Analysis (PCA), we identified that agricultural anthropogenic use had the greatest influence on territorial expression. The reported scenario indicates a trend of gradual and continuous reduction of naturalness over the last 20 years. Additionally, the D2N index proved to be a useful tool to demonstrate both the anthropic impact, with the simplified scale, and the How to cite this paper: López, F.