The Yellow River Basin as a whole is in the mid- to late stage of industrial transformation and the rapid development stage of the regional economy. It is in general in the “siphon effect” stage where the agglomeration function is stronger than the diffusion effect, and in the period of intense competition in intraregional development. Medium/high-speed economic growth of high-quality is a prerequisite for the modernization and sustainable development of the Yellow River Basin. Based on a general analysis of the connotation and change of theories of high-quality development in the basin (region), this article explores the basic conditions and core strategies of high-quality development in the Yellow River Basin. The basic conditions of high-quality development are the local diversity and vulnerability of agricultural development, the loose nature of the economic links in the river basin, constraints from the stage of economic development and its internal differences, and lack of momentum of external investment and industrial transfer, among others. These particularities determine that the high-quality development of the river basin must manifest itself in a long-term, diverse, competitive, cooperative, and regional orientation. Therefore, the high-quality development of the Yellow River Basin needs to explore a core strategy of “overtaking by curves”: (1) With the development of smart society and globalization, the region should seek high-quality growth, that is, continue to explore new industrialization models in the region that are suitable for national needs and local characteristics, and build localized industrial clusters/chain to enhance comprehensive competitiveness; (2) Explore new models of synergy under the premise of homogeneity, plan river basin coordination and improve coordination mechanisms, and seek a new urbanization model of localization, including localized population urbanization strategy and urban-rural coordination model, especially the continued migration of rural population to river valleys/basins, plains, and towns based on land transfer. Improve labor productivity, paying attention to water resources and infrastructure construction, and so on; (3) Implement the “center breakthrough” system, seek the spatial reconstruction of the drainage basin led by the centers, promote the healthy development of central cities and urban agglomerations, and promote high-quality development. In general, the high-quality development of the Yellow River Basin is a long-term exploration process of at least 20-30 years.