Analysis of the coseismic differential response of adjacent monitoring wells is an important way to study the coseismic response mechanism of groundwater. On February 3, 2020, the Qingbaijiang earthquake caused the abnormal changes of groundwater levels and water quality in the monitoring wells of Longquanshan. In this paper, the coseismic differential response characteristics of two adjacent monitoring wells are analyzed by using the automatic monitoring data of various hydrochemical components and water levels. Based on the coupling response characteristics of hydrochemical components and water levels, the mechanism of differential response of hydrochemical components and water levels is discussed. In the case of the same energy density, the water level variation amplitude of well ZK1 is larger than that of well ZK6, which indicates that ZK1 is more sensitive to the earthquake response than ZK6. The earthquake mainly caused the discharge of the groundwater (
Eh<0) from the second aquifer (
\rmNH_4^+ and
\rmNO_3^- ) to ZK1, while the groundwater (
Eh>0) from the first aquifer (high concentration of Cl
−, TDS, and pH) to ZK6. The discharge and mixing of water from different aquifers into the wells are the reason for the different response of chemical components of groundwater in these two wells. According to the trends of chemical components and water levels after the earthquake, rock mass under seismic action of undrained volume change is the main cause of groundwater water status step change, that is, plastic deformation and permanent change in permeability occurred in the second aquifer around well ZK1, and no permanent change in permeability but elastic deformation occurred in rock mass around well ZK6.