Climate and land-use changes have significant impacts on Iranian forests in mountainous areas, affecting soil quality, vegetation growth, and biodiversity. This research study suggests that the changes lead to soil organic carbon reduction, increased risk of habitat loss, and extinction risk for various species, particularly in regions such as Zagrosa and Alborz mountainous areas. The results reveal a wide-spread agricultural expansion (27,000 km2) and a significant cultivation intensification (48,000 km2). At the same time, we observe a substantial decline in total water storage that is not represented by a decrease of meteorological water input, confirming an unsustainable use of groundwater mainly for agricultural irrigation. As consequence of water scarcity, we identify agricultural areas with a loss or reduction of vegetation growth (10,000 km2), especially in irrigated agricultural areas under (hyper-)arid conditions. In Iran’s natural biomes, the results show declining trends in vegetation growth and land cover degradation from sparse vegetation to barren land in 40,000 km2, mainly along the western plains and foothills of the Zagros Mountains, and at the same time wide-spread greening trends, particularly in regions of higher altitudes. Overall, the findings provide detailed insights in vegetation-related causes and consequences of Iran’s anthropogenic drought and can support sustainable management plans for Iran or other semi-arid regions worldwide, often facing similar conditions.