Mediterranean landscapes, historically shaped by diverse ecological and socio-economic forces, are increasingly vulnerable to land degradation (LD), posing significant challenges to sustainability. While LD was once considered a challenge confined to arid regions, its impact has spread to temperate areas such as southern Europe. In Italy, LD has intensified over the past decades due to the interaction of climate change, land-use shifts, and human pressures, threatening sustainable development and rural economies. However, assessments at the national scale over time remain scarce. This study provides a detailed assessment of changes in sustainability and sensitivity to LD in Italy from 1960 to 2020 using the Environmental Sensitive Area Index. Our findings show a significant increase in LD-prone areas, especially in southern Italy and the major islands. Additionally, reductions in rainfall in northern lowland regions, combined with agricultural intensification and population density, have escalated vulnerability, paralleling southern conditions. These results highlight the intersection of environmental sustainability with broader political and economic processes, including agricultural policy, European integration, and peri-urban development. As the European Union pushes for sustainability, using means such as the Sustainable Development Goals, the Green Deal, the Farm to Fork, and other initiatives, addressing LD is crucial to safeguarding Mediterranean landscapes. Therefore, this study serves as an early warning, stressing the need for integrated, forward-looking policies to combat LD throughout the advanced Mediterranean economies, supporting regional resilience and sustainable development.