Both the topography and stratigraphy of slopes significantly affect the ground motions of slopes during earthquakes, and oblique incidence of seismic waves can further aggravate amplification. This study aims to parametrically explore the combined effects of the topography and stratigraphy of layered rock slopes on seismic amplification subjected to vertical and oblique propagating waves and provide qualitative and quantitative insight into this phenomenon. The spectral element method used to obtain the seismic response of slopes is introduced and verified by two examples. The influences of the slope angle, material properties of the layers, surface layer conditions, and incident angle of the seismic waves on the seismic amplification are then investigated. The results indicate that the peak horizontal and vertical amplification factors for layered rock slopes subjected to vertical and oblique incidence of seismic waves are in the ranges of 1.3–7.6 and 0.3–5.2, respectively. Among the various factors, the thickness and shear wave velocity of the surface layer of slopes have the greatest influence on the amplification effect, especially for obliquely incident waves. At oblique incidence, the maximum horizontal and vertical normalized acceleration amplification factors for the soft-surface-layer slope are 4.4 and 7.4 times greater than those for the hard-surface cases, respectively, whereas at vertical incidence, these values are only 2.8 and 4.3, respectively. When the impedance ratio between the surface layer and the underlying layer is 0.5 (i.e., the soft surface layer), unusual vertical amplification is observed where the maximum vertical amplification factor reaches 5.2. The findings of this study may provide useful reference and guidance for the seismic design of slope engineering and building structures near slopes.