People's health is the basis for the progress of social civilization and an important symbol of national prosperity and national strength. Using the entropy method, spatial autocorrelation, spatio-temporal geographic weighted regression and other methods, we conducted a comprehensive evaluation of the high-quality development level of public health in Guizhou Province from 2011 to 2020 and an evolutionary analysis of the spatio-temporal divergence. The results revealed four key aspects of the state of public health in Guizhou Province. (1) The overall level of public health is constantly improving, but structural imbalance is prominent. (2) From the spatial dimension, the spatial differences in the level of public health have gradually moved from significant to a state of equilibrium. The northeastern cities were more strongly driven by the radiation of the peripheral cities, while this effect was weaker in the southwestern cities. From the time dimension, the spatial pattern shows a clear gradient, with a faster vertical growth rate. (3) The overall spatial correlation of the level of public health is weak, with more cold spots than hot spots, showing a distribution pattern of “strong in the northeast and weak in the southwest”. (4) The new rural cooperative medical care participation rate, (rural) per capita health expenditure, and the electronic health record creation rate have become the most important drivers affecting the high-quality development of public health in Guizhou Province.