Earthquakes are one of the main factors inducing large-scale loess bedrock and especially loess-mudstone landslides in Western China, and these types of landslides are often closely related to fault zones. To study the influence of high anti-dip angle fault zones (HADAFZs) on loess-mudstone slopes (LMSs) during earthquakes, a scaled model with an HADAFZ of 80° using a shaking table test and numerical calculation, subjected to earthquake waves, was applied to reveal the rules of seismic response and failure characteristics. The acceleration dynamic response had a top surface amplification effect on the slope surface, an accelerated increase effect on the slope-surface hanging wall, an amplification effect away from the free slope face in the loess stratum, and a combination of elevation and lithology effects in the vertical section. At the loess–weathered mudstone (L–W) and weathered mudstone–mudstone (W–M) interfaces, the amplification response of a hanging wall was the largest, fault zone was the second, and foot wall was the smallest. Furthermore, the key value of input peak ground acceleration (PGA) for the dynamic response was a = 0.3 g. The hanging wall amplification effect became apparent while a > 0.3 g, and cracks appeared on the surface of the slope. The dynamic response of the soil pressure was influenced by the hanging wall amplification effect and had a positive correlation with the thickness of the overlying layers, both in the loess stratum and at the L–W interface. However, the dynamic soil pressure maximum variation (DSPMV) on both sides of the fault zone was larger than that in the fault zone. The development of an HADAFZ in the LMS hindered the integral connection of the potential sliding surface and restricted the overall sliding failure of the slope during the earthquakes.