The present study focuses on investigating the effects of soil rotated anisotropy and spatial variability on slope failure in seismic conditions. The random finite element method aided by subset simulation is implemented, which ensures an efficient quantification of both the probability of failure and its associated consequence of failure. Several slope angles of gentle and steep slopes and soil properties that lead to a low probability of failure were selected for parametric studies. The comprehensive parametric studies of seismic slope stability analysis consider various factors such as slope inclinations, seismic coefficients, scales of fluctuation, and orientations of the major principal scale of fluctuation (i.e., the rotation angle of random field). The results underscore the importance of considering the combined effects of soil anisotropy and the orientation of the major principal scale of fluctuation for designing both gentle and steep slopes under seismic conditions and emphasize that care must be given to ensure the worst-case scenario is considered. Visual observations of failure mechanisms of gentle and steep slopes under seismic conditions were also shown to be very helpful in interpreting the variation of probability of failure due to soil spatial variation.