Separated analyses are available for evaluating slope stability after seismic shaking and rainfall. However, the combined effect of seismic shaking and rainfall water seepage on slope stability has not yet been well studied. In this study, the stability of the designed 30° and 45° slopes was analyzed under static, rainfall seepage, and seismic conditions. The soil shear strength reduction method was adopted to determine the factor of safety (FS) of the slope through the plane strain model of the finite difference method. The factor of safety and failure mode of the slope were studied for the interaction mechanism of seismic shaking and rainwater seepage. The numerical analysis results indicate that the soil friction angle has stronger effects on the slope stability than the soil cohesion does under the same slope conditions. The failure surface observed for biaxial seismic shaking was different from that observed for uniaxial seismic shaking. The combination effects of multi-axial seismic shaking must be considered when analyzing the failure mode of the slope. Seismic shaking after rainwater seepage results in a low FS and changes the failure mode of the slope. The FS continuously decreased with the biaxial and post-rainwater seepage seismic shaking of the slope. Seismic analysis after rainwater seepage is important for safety evaluation and disaster prevention in landslide-prone areas.