Policy and decision making in the context of sustainable development requires rapid, effective and efficient access to and integration of appropriate current information from a wide range of sources, including land cover changes information derived from remotely sensed data. Geomorphic factors, such as altitude, slope, aspect and lithology presented in the area comprise the main parameters, including the climate, influencing the distribution of land cover. The use of a Geographic Information System (GIS) allows further spatial analysis of the data derived from remotely sensed images and digital terrain spatial models, and analysis of the impact of land cover change on regional sustainable development. The remotely sensing data used in this study was Landsat 5 TM and Landsat 7 ETM+ images. Normalized Difference Vegetation Index (NDVI) and Selective Principal Component Analysis (SPCA) techniques were applied to detect land cover change and especially vegetation changes from multitemporal satellite data. The area under study is the basin of River Sperchios, which covers an area of some 1.780 km2, is approximately 60-80 km long, 20-30 km wide with its southern and western flanks characterized by high elevations and steep slopes, whilst its northern flank presents lower elevations and more gently slopes. The conclusions obtained show that extensive land cover changes has occurred in the last decades as a result of both natural forces and human activities, which has in turn impacted on the regional sustainable development. The results thus provide very useful information to local government for decision making and policy planning.