The instability of slopes caused by ground vibration will often bring great casualties and serious property losses. Hence, it is of great practical significance to evaluate the reliability of slope reasonably and accurately for the seismic design and the actual disaster prevention project. A lot of engineering practice and previous studies show that the spatial variability of soil and the vertical seismic both have an obvious influence on the reliability of slope among many factors affecting the reliability of slope. But currently, there is still little research considering the influence combined these two essential factors simultaneously. Therefore, this paper aims to study the influence of vertical ground motion on the reliability of two-dimensional slopes while considering the spatial variability of soil parameters. The change of factor safety due to the different direction sets of seismic (horizontal seismic, and combine both of the horizontal one and vertical one) has been mainly reported. Finally, based on the probability density evolution method, the dynamic reliability analysis and safety evaluation of the 2D slope is carried out.