The Mekong River's abundant natural ecosystems supports the lives of coastal residents in numerous ways and plays a major role in Southeast Asia. Soil erosion is a major environment problem and can easily lead to land degradation and sedimentation. In this study, we applied the Universal Soil Loss Equation model to explore soil erosion and spatial distribution characteristics of the Mekong River Basin. We also combined the Information Entropy method to explore the dominant factors of soil erosion. The results showed that the average soil loss is 1.98×10³ t km^-2 a^-1. There are different levels of soil erosion in about 40% of the area. Serious erosion mainly comes from elven catchments (M4-M7, M9, T4-T6, T8, T10, and T20). Land cover type, slope, and altitude are dominant factors influencing soil erosion in the basin. Shrub and bare/spare vegetation areas are subject to strong and extreme erosion. The mean soil loss first increases and then decreases with increasing slope, and it is the same with mean soil loss and altitude. The major characteristics of extreme erosion areas are: bare/spare vegetation and shrub, sea level range of 500 m to 2000 m, and slope range of 8 to 25°. Finally, based on the Priority Theory, the priority governance order of the Mekong River Basin was ranked and graded. It was divided into four grades and there are three tributaries belonging to the first grade. Our results could provide a scientific reference for future planning and management of soil and water conservation in the Mekong River Basin.