Land-use change is the main component of regional environmental change, while protected areas represent a direct land use policy to prevent its potentially negative effects on biodiversity and environmental services. We combined an analysis of trends in land use and human demography with trends in creation of protected areas during the last three decades in northwestern Argentina, a subtropical region including a wide range of environments. The eighty nine administrative analysis units of the region were classified into four ecological groups based on their percentage of cover by the six eco-regions of the study area: (1) “Dry valleys”; dominated by Middle-elevation deserts; (2) “Highlands”, dominated by High-elevation alpine zones and plateaus; (3) “Humid ecosystems”, dominated by Foggy grasslands and Humid forests, and (4) “Dry forests”. Between 1970 and 2002, human population became concentrated in urban areas and land use trends varied greatly among the four ecological groups. Agricultural area decreased in the Highlands and increased in the other regions, particularly in the Dry forests. Domestic animals decreased in Humid ecosystems, Highlands and the Dry valleys; and remained constant in the Dry forests. Several protected areas were created, but most of them were established in regions undergoing a decreasing intensity of land use. Overall, the analysis shows that agricultural production is becoming concentrated in the areas more suitable for modern agriculture while marginal agriculture areas and, particularly, extensive grazing are decreasing. The creation of protected areas reflects the decreasing opportunity costs of marginal areas and is failing to protect the eco-regions most threatened by current land-use trends.