With the development of mining, the hydrochemical environment has changed in the Renlou coal mine, Anhui Province, China. It will be of great significance to coal mine safety production by exploring the temporal and spatial evolution law of hydrochemistry of main water-inrush aquifers in Renlou coal mine under the effect of mining. Groundwater samples from three main water-inrush aquifers in different periods were collected to analyze their principal components and establish the discrimination model of water-inrush source. The first and second principal components with eigenvalues greater than 1 were selected, in which the first principal component represents sulfate dissolution and pyrite oxidation, and the second principal component represents desulfurization and cation alternating adsorption. The evolution law of hydrochemical environment was analyzed by combining the distribution characteristics of principal component scores with the spatial location of misjudged groundwater samples. The results show that (1) Quaternary aquifer is greatly affected by mining, and the hydraulic connections with Carboniferous limestone aquifer in the central region leads to two misjudged groundwater samples in the discriminant model. (2) Permian sandstone aquifer is to a certain extent affected by mining, which shows a relatively closed hydrogeological environment in most areas of coal mine and an opened environment in some areas with time. There are five misjudged samples in the discriminant model due to hydraulic connections with the Quaternary aquifer and carboniferous aquifer in some areas. (3) Carboniferous limestone aquifer is controlled by typical faults and collapse columns, and mining has a slight influence on it. In the central area, there are hydraulic connections with the Quaternary aquifer and the Permian sandstone aquifer due to the collapse columns, which lead to four misjudged groundwater samples in the discriminant model.