The study aims to evaluate soil erosion and investigate its spatial distribution by applying two empirical models, namely the Erosion Potential Model (EPM), also known as Gavrilovic method, and the RUSLE model at Venetikos River catchment, the largest and most important tributary of Aliakmonas River, located at Western Macedonia, Northern Greece. To that end, a GIS-based evaluation is adopted, leading to a more accurate result. The models were implemented both annually and inter-annually. The results were compared with the catchment’s “actual” mean annual sediment yield, computed by the sediment discharge measurements conducted on a monthly basis at its outlet, namely Grevena Bridge, by the Greek Public Power Corporation (PPC) during the time period from 1965 to 1982. The Gavrilovic model slightly underestimated the outcome in comparison to the RUSLE methodology which attributed relatively more accurate results, yet performed quite similarly at both time scales. The two approaches simulated the phenomenon quite satisfactory, showing acceptable precision and allowing identification of the most susceptible to erosion and degradation areas, constituting important predictive tools for soil and environmental management in this region.