Human appropriation analysis allows interrelating ecological and socioeconomic dimensions to be applied during the development of management strategies for increasing the sustainability of land uses. However, the design of such management strategies requires data reflecting site-specific conditions at sub-national levels. In this study, we assessed the dynamics of human appropriation using an exergy-based net primary production (HANPPEX) indicator. The results depicted positive (5–10 MJex/m2.y) HANPPEX changes for cropland areas in both regions. The harvested biomass and land-use changes were identified as responsible for high HANPPEX, which varied significantly between land cover types. In particular, cropland and urban/industrial yielded the highest HANPPEX compared to other land cover types. Accordingly, the land cover transition toward urban and agriculture land uses increased the HANPPEX for Ñuble and Biobío. The main HANPP differences found between regions were related to their socioeconomic characteristics as well as to the heterogeneity of land-use types, biomass structure, and regional biomass demand. Our findings provide insights on the magnitude and direction of NPP changes associated with human appropriation at the regional level, allowing a more detailed understanding of the efficiency with which humans utilize terrestrial natural resources. Display omitted •Strategies for better land use sustainability need regional human appropriation data.•We used the exergy-based net primary production (HANPPEX) indicator for HA dynamics.•Urban and croplands had high HANPPEX upon spatial analysis of two Chilean regions.•Regional differences were from socioeconomic, land-use type, and biomass features.•Understanding regional HA-related NPP profiles may optimize natural resource use.