One of the most important natural processes, with significant environmental impacts, is soil erosion. The aim of this paper is to evaluate and assess the erosion vulnerability of the geological formations constituting Sperchios River basin, in Eastern Central Greece, as well as to distinguish and locate the areas of such risk and estimate it. The developed methodology in this paper is based on Multi-Criteria Evaluation (MCE), with the implementation of Weighted Cartographic Overlay (WCO) technique in Geographic Information Systems (GIS) environment. By applying this method, an attempt was made to combine a set of factors, such as geological-hydrogeological characteristics, morphological slopes and hydrographic texture (causative factors of the phenomenon) along with rainfall (triggering factor) and land cover/use (competitive factor). The weighted combination of these factors defines the vulnerability of the formations in the area of interest. The main results of the methodology are two thematic maps of erosion vulnerability of Sperchios basin’s formations, one that does not include land use/cover factor and one with current existing conditions of the basin (co-evaluating land use/cover). In the first case, 36% of the basin surface undergoes high erosion vulnerability, while 53% present medium vulnerability. These percentages reduced significantly in the second case (3% is the high erosion vulnerability category and 38% the medium one), fact that proves the importance of vegetation in erosion restriction and protection of the geological formations consisting the Sperchios River basin.