The Yellow River Basin is an important ecological barrier for China; the ecology there is sensitive and fragile and ecological problems are severe in some regions. Therefore, it is necessary to conduct a systematic planning of ecological management and address prominent problems for the basin. To further promote the ecological protection and high-quality development of the Yellow River Basin, this article analyzes the major challenges regarding ecological protection in the region and summarizes the major problems there from the aspects of investment in ecological management, construction of ecological monitoring networks, and modernization of ecological management capacities. Based on this, we propose a strategic system framework for integrated ecological governance in the Yellow River Basin led by major projects. The integrated ecological governance should consider the spatial differentiation of upper, middle, and lower reaches and adhere to the principle of systematic design. Moreover, measures need to adapt to local conditions, and land and water should be linked for joint prevention and control. Additionally, major projects are required to lead the integrated governance, including mountain–river–forest–farmland–lake–grass–sand integrated protection, environmental pollution comprehensive control, and ecological management modernization projects. Considering the urgency and necessity of solving current ecological problems, we propose the following suggestions: (1) establishing an ecological management project library, (2) implementing major projects in stages and in batches, (3) conducting entire-process supervision and effectiveness evaluation of major projects, and (4) strengthening scientific and technological support for the major projects.