Water erosion in Tunisian semi-arid regions causes harmful effects by silting reservoirs and reducing agricultural lands and soil fertility. Several factors are involved in the erosion process: rain erosivity, soil fragility, and degraded land cover on steep slopes associated with the intensification of inappropriate human practices. Thus, identifying erosion vulnerable sub-watersheds based on the assessed soil loss rate is very important to apply suitable conservation measures. The current research aimed to prioritize risky areas in the Lakhmess watershed, north-west Tunisia via the Soil Erosion Assessment using Geographical Information System (SEAGIS) model. To prioritize sub-watersheds vulnerable to soil erosion and sediment yield, the Lakhmess watershed, covering an area of 162 km2, was divided into 16 sub-watersheds (L1–L16), according to the hydrographic network. Then, the mean annual soil erosion rate and the mean annual sediment yield in the watershed were estimated by integrating the Revised Universal Soil Loss Equation (RUSLE) and the Sediment Delivery Ratio (SDR) in the SEAGIS model and their spatial distribution was determined. The obtained results indicate that the estimated average annual soil erosion rate is 4.2 t/ha/y and the annual sediment yield is 2.6 t/ha/y. Maner's SDR model was selected as the best model for estimating SY, with standard error, standard deviation, and coefficient of variation values of 0.75%, 0.01, and 0.45%, respectively. The prioritization of the Lakhmess sub-watersheds based on the estimated soil loss rate reveals that among the 16 sub-watersheds, three sub-watersheds (L10, L12, and L15) were identified as being in a very high priority soil erosion class. The high soil erosion rate and sediment yield in these sub-watersheds is explained by the steep slope and a high rainfall erosivity factor. Six sub-watersheds (L2, L4, L5, L6, L7, and L16) were found to belong to a very low priority soil erosion class, as they are characterized by a very gentle slope, which appears to be an extremely determining factor. These findings constitute a basis for decision makers to plan effective conservation measures to conserve agricultural lands, soil, and water resources in northwestern Tunisia.