During the 1999 Athens earthquake, the town of Adàmes, located on the eastern side of the Kifissos river canyon, experienced unexpectedly heavy damage. Despite the particular geometry of the slope that caused significant motion amplification, topography effects alone cannot explain the uneven damage distribution within a 300-m zone parallel to the canyon’s crest, which is characterized by a rather uniform structural quality. In this article, we illustrate the important role of soil stratigraphy and material heterogeneity on the topographic aggravation of surface ground motion. For this purpose, we first conduct an extensive time-domain parametric study using idealized stratified profiles and Gaussian stochastic fields to characterize the spatial distribution of soil properties, and using Ricker wavelets to describe the seismic input motion; the results show that both topography and local soil conditions significantly affect the spatial variability of seismic motion. We next perform elastic two-dimensional wave propagation analyses based on available local geotechnical and seismological data and validate our results by comparison with aftershock recordings.