Through the sample measurement of the panel data of 59 prefecture-level cities in the Yellow River Basin from 2003 to 2017, this paper analyzes and discusses the characteristics of temporal and spatial evolution, regional gaps and improvement paths of the Yellow River Basin in ecological protection and high-quality development. The results show that the comprehensive level of ecological protection and high-quality development is low, there is a large room for improvement, and it has obvious characteristics of periodic fluctuations over time. The high-value areas of the comprehensive level of ecological protection and high-quality development are mainly distributed in the Yellow River Basin. Upstream and downstream cities have the characteristic of “dual-core leadership” spatial agglomeration, while midstream cities are always in the “low-level stable growth trap” stage; the overall regional gap is large, and the inter-regional gap is the main reason for the overall regional gap; per capita output, opening to the outside world, human capital drive the improvement of the comprehensive level of ecological protection and high-quality development, and government intervention and environmental regulation drive the reduction of its comprehensive level. It is recommended to strengthen regional linkage to achieve a coordinated improvement in the quality of development, adhere to local conditions and identify a path to highlight regional characteristics, highlight linkage effects to accelerate regional economic development, optimize the power system to achieve steady growth in the regional economy.