Abstract: To reveal the driving factors for the distribution of cities and towns in the areas south to the Yangtze River from the mid-18th century to the mid-20st century as well as their spatio-temporal evolutionary process, a spatio-temporal evolution model (GWR model) of the variation in the number of cities and towns was established by taking the number of cities and towns during 1736-1850 and during 1851-1949 as dependent variables and their corresponding population scale, population density, river density, and altitude median as independent variables, respectively. The kernel density map and the industrial area map were combined to investigate the effects of industry on the deve-lopment of cities and towns. The research results show the following. During 1736-1850, distribution of cities and towns in the areas south to the Yangtze River presented a spatial agglomeration, but during 1851-1949, the spatial agglomeration was reduced. The population growth in the areas south to the Yangtze River drove the stable increase in the overall number of cities and towns. During 1736-1850, the river density significantly drove the increase in the number of cities and towns at the eastern part of the areas south to the Yangtze River. During 1851-1949, the river density in the eastern part of the areas south to the Yangtze River turned out to be negatively correlated to the increase in the number of cities and towns in this area. During 1851-1949, the river density in the areas around Taihu Lake and the northwest of the areas south to the Yangtze River significantly drove the increase of cities and towns. The explosive increase of towns and cities in areas excluded in the analysis of GWR model was closely related to local cotton planting industry.