Major damage has been reported in hilly areas after major earthquakes, primarily because of two special conditions: the variation in the seismic ground motion due to the inclined ground surface and the irregularities caused by a stepped base level in the structure. The aim of this study is to evaluate possible differences in the responses of Chilean hillside buildings through numerical linear-elastic and nonlinear analyses. In the first step, a set of response-spectrum analyses were performed on four simplified 2D structures with mean base inclination angles of 0°, 15°, 30°, and 45°. The structures were designed to comply with Chilean seismic codes and standards, and the primary response parameters were compared. To assess the seismic performance of the buildings, nonlinear static (pushover) and dynamic (time-history) analyses were performed with SeismoStruct software. Pushover analyses were used to compare the nonlinear response at the maximum roof displacement and the damage patterns. Time-history analyses were performed to assess the nonlinear dynamic response of the structures subjected to seismic ground motions modified by topographic effects. To consider the topographic modification, acceleration records were obtained from numerical models of soil, which were calculated using the rock acceleration record of the Mw 8.0 1985 Chilean earthquake. Minor differences in the structure responses (roof displacements and maximum element forces and moments) were caused by the topographic effects in the seismic input motion, with the highly predominant ones being the differences caused by the step-back configuration at the base of the structures. High concentrations of shear forces in short walls were observed, corresponding to the walls located in the upper zone of the foundation system. The response of the structures with higher angles was observed to be more prone to fragile failures due to the accumulation of shear forces. Even though hillside buildings gain stiffness in the lower stories, resulting in lower design roof displacement, maximum roof displacements for nonlinear time-history analyses remained very close for all the models that were primarily affected by the drifts of the lower stories. Additionally, vertical parasitic accelerations were considered for half the time-history analyses performed here. The vertical component seems to considerably modify the axial load levels in the shear walls on all stories.