Rural transformation development is an important part of rural revitalization, and the study of spatial–temporal differentiation characteristics and the driving mechanism of rural transformation development can provide a decision-making reference for formulating rural revitalization programs according to local conditions. Taking the Yangtze River Economic Belt as the research case, we constructed an evaluation system of rural transformation development in the dimension of “population, land and industry”, and the entropy TOPSIS method, spatial autocorrelation model and geographic detector model were used to reveal spatial-temporal differentiation and the driving mechanism of rural transformation development in the Yangtze River Economic Belt from 1978 to 2018. The results showed that (1) rural transformation development has been significantly unbalanced in the Yangtze River Economic Belt, and rural transformation development showed a weak distribution. Moreover, in terms of dimensions, the land use transformation level > population development transformation level > industrial development transformation level. (2) On the global, rural transformation development presented a spatial distribution trend of club convergence. On the local, the H(High)–H(High) type was mainly distributed in Shanghai City and the southern part of Jiangsu Province, and it evolved to Hangzhou-Shaoxing-Ningbo and Wanjiang City Belt; the L(Low)–L(Low) type was mainly concentrated in the western part of Sichuan Province and in the southwest of Yunnan Province. (3) Natural conditions, economic social development, traffic accessibility, policies and systems were the leading factors affecting rural transformation development in the Yangtze River Economic Belt. The influences of economic social development and traffic accessibility on rural transformation development were increasing, and policy factors had an important guiding effect on rural transformation development, and the influence of natural conditions on rural transformation development has weakened. This study can provide a practical reference for rural transformation and rural revitalization in the Yangtze River Economic Belt.