Abstract: This paper studies the spatial and temporal evolution of regional economic differences and the stage of economic development in the Yangtze River Economic Belt from 1994 to 2017 based on ESDA spatial statistics, variation coefficient and gini coefficient. The spatial heterogeneity of factors affecting economic development differences are analyzed by ordinary least squares (OLS) and geographical weighted regression model (GWR). The results show that: (1) The economic difference of Yangtze River Economic Belt changes from strong agglomeration to weak agglomeration. It has gone through four stages of economic development: germination, rise, prosperity and transformation. It presents the stage characteristics of self-construction and development, regional development, convergence and competition, and industrial transformation. Regional economy presents the situation of “equilibrium unbalance- gradual equilibrium”. (2) The Yangtze River Delta urban agglomeration is the core hot spot area, while Chengdu-Chongqing urban agglomeration and central Yunnan urban agglomeration are the core and sub-core cold spot areas. Economic development experiences alternation of agglomeration effect and trickle-down effect. Regional economic disparities expand first, then decrease, and tend to be balanced, which conforms to the law of “unbalanced growth theory”. (3) Geographically weighted results show that population agglomeration, industrial structure, foreign investment, government regulation and control, traffic development, science and technology education, financial situation are the positive internal driving forces of the spatial and temporal evolution of regional economic development. Development costs and terrain conditions are constraints. Industrial structure is the core driving force. Science and technology education is an important driving force. Terrain condition is the basis of development. When formulating regional development policies, we should consider the heterogeneity and particularity of different administrative regions and driving factors.