With the rapid development of the economy and the enhancement of human activities, the ecological environment has been significantly damaged in recent years. How to scientifically manage the threatened ecological environment is of great significance. The Yellow River Basin (YRB) is not only an essential ecological security barrier but also an essential area for population activities and economic development in China. However, there are many environmental problems, such as ecological degradation, land desertification, and water pollution. It is extremely urgent to carry out scientific and efficient ecological zonal management in YRB. In this paper, Morphological Spatial Pattern Analysis (MSPA) and the New Modified Remote Sensing Ecological Index (nmRSEI) were used to extract the ecological sources and construct the Ecological Security Pattern (ESP). In addition, the ecosystem vulnerability of the YRB was evaluated in terms of habitat condition, ecosystem structure, and ecosystem services. It was divided into four ecological management zones using the four-quadrant model based on the ecosystem vulnerability index (EVI) and nmRSEI results. The results indicated that the ecological source of the YRB covers an area of 153,680 km2, which is primarily located in the southeastern and upstream areas. Qinghai had the largest ecological source area (36.53%), followed by Gansu (19.43%) and Shaanxi (16.51%). 507 ecological corridors were extracted, and 82 barriers and 142 ecological pinch points were identified using Linkage Mapper. In addition, the four types of ecological management zones have significant and interspersed spatial variations in distribution, which together constitute the ecological protection and management system of the YRB. Based on the objectives of the four management zones and the comprehensive plan of the YRB, the economic belt along the Yellow River and the six core management nodes were constructed, and measures for comprehensive management were proposed. The perspective and research framework proposed in this study can provide a scientific foundation for the ecological governance and high-quality development in the YRB, as well as an applied reference for the ecological management of other similar watersheds around the world.