The world’s major river basins witnessed the history of the development of human economic division of labor. Today’s global environmental changes and economic integration have a profound impact on the relationship between the opening-up of river basin economic systems and their sustainable development. Through a regional economic geography analysis guided by modern systems science methods, this study conducted case descriptions and indicator comparisons of selected international river basins in Asia, Europe, North and South America, and Africa. The findings show that the opening-up factors have a complex effect on the operational parameters of the economic systems of the river basins, which leads to the diversification of the pattern and development path of the economic systems of the river basins. The global river basin economic system form the benign teraction between opening-up and sustainable development through the combined action of independent opening-up, innovation, coordination, adaption and sharing, which can provide the Yellow River Basin with experiences for realizing high- quality sustainable.