Accelerated soil erosion caused by water is one of the most widespread problems affecting environmental quality, agricultural productivity, and food security in many countries. These issues tend to cause more severe impacts on developing countries, especially in the tropical highland areas. Therefore, this study was conducted in the Prek Thnot Basin, a sub-catchment of the Mekong Basin in Cambodia, to (1) simulate sediment yield at the outlet by using Soil and Water Assessment Tool (SWAT); and (2) identify productive sediment yield area of the catchment. The SWAT model was selected due to the availability of data and the capability to represent the reality of hydrological and water quality processes, which is the best method to determine the answer to the study objectives. In response, the SWAT provided an actual performance in each calibration and validation process of both runoff and sediment yield. The annual soil erosion in most parts of the study area range from approximately 100 to more than 1400 tons/km2/y. This study indicated that the most erosive part of this study area covers 91.78 km2, which contributed to 1.64% of the whole watershed with a sediment yield of about 2206 tons/km2. In addition, the assessments of sediment deposition and erosion using Modified Universal Soil Loss Equation (MUSLE) indicated the annual sediment load along the flow direction of the mainstream, from the upper river to the outlet of the Prek Thnot river basin, about 0.2 million tons. As a result, the middle to the upstream of the watershed is the most sensitive to produce the sediment yield.