The harmonious balance between economic development and the eco-environment is one of the essential ways to promote the high-quality development of the Yellow River Basin, which is of great practical significance to the high-quality development of regional economic integration and the healthy and sustainable ecosystem. This study takes 379 districts and counties in the Yellow River Basin as the research objects. The decoupling relationship between economic development and eco-environmental pressure from 1990 to 2018 was dynamically analyzed based on the Entropy-TOPSIS comprehensive evaluation method and the Tapio decoupling model. We also introduced the structural decomposition model to explore the driving factors affecting the eco-environmental pressure, and used the PCMCI algorithm to infer the causal association paths driving the decoupling of economic development and eco-environmental pressure. The results demonstrate that:(1) 70% of the districts and counties are under low pressure in the Yellow River Basin, but the eco-environment in the Inner Mongolia, where the economy has developed rapidly due to the endowment of resource conditions, still carries high pressure. (2) The eco-environmental pressure is mainly driven by technical effects and economic effects. The driving effect of technology promotes the economic output and reduces the eco-environmental pressure, while the driving effect of the economy is more prominent in the middle and lower reaches of the Basin. (3) 68.34% of the districts and counties have achieved effective decoupling between economic development and eco-environmental pressure (strong decoupling and weak decoupling) in the Yellow River Basin. The total economic growth has reduced the pressure on the eco-environment load, but the type of decoupling between economic development and eco-environmental pressure is in dynamic changes. The districts and counties with strong or weak decoupling should be prevented from falling back to negative decoupling. (4) The demographic factors represented by rural population and urbanization rate effectively drive the decoupling of economic development from eco-environmental pressure in the Yellow River Basin. The rural population has the highest frequency of causality with the decoupling index and the urbanization rate has the most incredible causal intensity with the decoupling index. The agricultural technology factors dominate the decoupling of economic development from eco-environmental pressure in the largest number of districts and counties, and the diversification and intensification of farming structures alleviate the pressure of economic development on the eco-environment. The research has an implementable practical value for improving the sustainability of high-quality economic development and eco-environment protection.