The “Qinling-Huaihe Line” is the recognized geographical boundary between north and south China. In the context of a widening north–south gap, the large-scale population flow and the implementation of the regional coordinated development strategy, the north–south differentiation of the Chinese population requires further investigation. This study is based on national census data and uses quantitative methods, such as the centralization index, coefficient of variation, hot spot analysis and geodetector, as research methods. This study takes the Qinling-Huaihe Line as the dividing line and aims to extensively explore the spatial differentiation, evolutionary characteristics, and influential factors of the populations on both sides. The main conclusions are as follows: ① From 1982 to 2010, the population share ratio on the south and north sides of the Qinling-Huaihe Line remained at 58:42, showing a distribution pattern of “South more and North less”. ② The area within 200 km from the Qinling-Huaihe Line is a transition area with a stable distribution of the populations on both sides. ③ From 1982 to 2010, the concentration of the population distribution gradually increased on both sides, and the concentration of population on the south side was higher; the characteristics of population growth had significant spatial differences between the two sides. ④ The results calculated by the geodetector method show that socioeconomic factors are the main factors causing the spatial differentiation of the populations, while physical geographical environmental factors have a smaller influence and their influence continues to decrease.