Detailed study of the response of pipelines during seismic excitation can help reduce physical and financial losses during and after an earthquake. The current research investigated the seismic behavior of pipelines passing through variations in topography using two-dimensional and three-dimensional modeling. Their behavior has been modeled at the crest and toe of a slope and during longitudinal passage through the topography. The effects of the soil stiffness, diameter-to-thickness ratio of the pipeline, height-to-half-width ratio (shape factor), and input wave characteristics on the performance of the pipeline have been investigated. The results indicate that topographic effects can increase the strain on pipelines and the factors studied are crucial to accommodating this potential hazard.