Taking the down-slope with weak strata in the south of Fushun west open-pit mine as the reference prototype, numerical simulations of the down-slope with weak strata were conducted through FLAC3D software, which included the simulation of actual ground motion and ground motion input, the boundary conditions of slope model, rock mass parameters, and grid model division. The response rule of down-slope with weak strata under an earthquake was investigated by analyzing the acceleration and velocity of the monitoring points. The results revealed that: (1) The thickness of the weak layer is a critical factor affecting the response characteristics of the slope with a single weak layer under an earthquake, and it has a greater impact on the stability of the slope under earthquake load than the dip angle of a single weak layer. (2) Based on the horizontal velocity of monitoring point 2# at the intersection of the weak layer and the slope surface, it was concluded that the thickness has a significant influence on the velocity in the X direction. (3) The failure response law at the intersection of weak layers and slope changes with an increase in slope height when analyzing the response law of the double weak layer characteristic slope under an earthquake. The acceleration amplitude and velocity change degree of monitoring point 3# with double weak layers are more noticeable than that of monitoring point 2#. The response law of the down-slope under an earthquake is related to the dip angle, thickness, number, and location of weak layers. Therefore, the coupling effect of earthquake and weak layer characteristics on slope stability should be thoroughly considered in the process of slope treatment and protection.