Abstract: High-quality development is the major task in building China’s socialist modernization. Based on the perspective of new development concept and safe development principles, this paper developed a high-quality development evaluation index system and measured the high-quality development level of the Yangtze River Economic Belt, urban agglomerations, and cities. Spatial statistics and analysis techniques were adopted to explore the characteristics and evolution of high-quality development at different scales in the economic belt. The results show that: (1) The high-quality development level of the Yangtze River Economic Belt has been improved significantly, but the absolute development gap has been widened in the past decade. (2) The high-quality development gap within and among the three major urban agglomerations in the Yangtze River Economic Belt was obvious, with the Yangtze River Delta Urban Agglomerations having the highest development level and the smallest internal gap. The Middle Reaches of Yangtze River and the Chengdu-Chongqing urban agglomeration have been improved rapidly, but the internal gap of the former has been narrowed significantly. (3) The level of urban high-quality development showed a decreasing trend from the lower reaches among cities of the Yangtze River Economic Belt to the upper reaches. And the high-value cities has been increased in the lower reaches, while the low-value cities has been improved in the middle and upper reaches. Based on the analytic results, this paper put forward certain policy suggestions to improve regional differences among different reaches, to optimize spatial structure of urban agglomerations, to promote high-quality development of cities through weak dimensions, and to strengthen institutional mechanisms of coordinated development.