The Yellow River Basin is an important ecological barrier and economic development area in China, but it faces some problems such as the degradation of its ecological quality and a lagging economic level. Promoting the high-quality development of the Yellow River Basin is the only way for China’s economic construction to enter into high-quality development, and an objective evaluation of the development quality of the study area is the premise for effectively improving this development quality. Based on panel data during the period of 2010–2022, a framework of drivers, pressures, state, impact, and a response model was used to build an index system. The index of high-quality development for each province in the Yellow River Basin was calculated using the entropy TOPSIS model. Further, the descriptive statistics method and standard deviation ellipse were applied to analyze the spatio-temporal characteristics of high-quality development in the study area, and the geographical detector and spatio-temporal geographical weighted regression model were employed to reveal the driving factors for this high-quality development in the Yellow River Basin. The results showed that (1) the high-quality development index of the Yellow River Basin was steadily improved over the study period, with an average annual growth rate of 3.024%. (2) The high-value area of the high-quality development level in the study area was distributed from northwest to southeast, with the high values of each subsystem tending to be spatially stable, as well as the spatial differences of the subsystems increasing. (3) The proportion of tertiary industry, per capita disposable income, rural–urban income ratio, per capita GDP, per capita highway mileage, and population were the main factors affecting the spatio-temporal evolution of high-quality development level in the Yellow River Basin, with average q values of 0.867, 0.938, 0.852, 0.781, 0.842, and 0.763, respectively. (4) Except for the negative effect of per capita GDP, the other five driving factors all had positive effects on the high-quality development level, with average values of 0.044, 0.068, 0.227, 0.064, and 0.215, respectively.