The Selenge River in Mongolia is the world's largest freshwater lake—Lake Baikal, the most important inlet river, and the ecological security of the basin is a matter of concern for the construction of the ecological barrier on the Mongolian Plateau and in northern China. In order to clarify the ecological safety status of the Selenge River basin, this paper proposes an assessment method and technical process based on the Pressure-State-Response (PSR) model, with a view to providing a reference for sustainable ecological management in the region through assessment applications. Firstly, we classify the land cover of Selenge River Basin and analyze the ecological status of Selenge River Basin with the official statistics of Mongolia. Further, based on the PSR model, a hierarchical analysis was used to assess the ecological safety status of the Selenge River basin. The results show that the real steppe within the Selenge River basin occupies the largest area of about 160,000 km², accounting for 53% of the total area, followed by the forest with an area of about 10 km², accounting for 32% of the total area, with a high vegetation cover. The ecological response and ecological state in the watershed are at a safer level, where the arable land area and the level of agricultural mechanization have a greater impact on the ecological state and ecological response. However, at the same time, there is a greater ecological pressure, and the area of land degradation and the stock of livestock are the main influencing factors that cause greater ecological pressure. In the future, policy regulation in these two aspects should be strengthened. In general, the ecological safety of the Selenge River Basin in Mongolia is at a relatively safe level and can be exploited moderately.