This paper investigates the analytical results of the seismic response of multi-span prestressed concrete (PSC) I-girder bridges under seismic loads. To perform numerical analyses, a three-span PSC I-girder bridge with a width of 12 m, a total length of 100 m, and a maximum span length of 40 m was modeled, and a virtual location was selected to consider the soil properties of the area where the bridge was constructed. The seismic load acting on the PSC I-girder bridge was applied in consideration of the soil properties around the pier and the wave passage effect of the bedrock in the artificial seismic load generated, according to the U.S. Nuclear Regulatory Commission (NRC) standard. The analysis results confirmed that the seismic load, with consideration of the soil properties and wave passage effect, generated the maximum response acceleration and bending moment at the deck of the bridge—152% and 232% greater than without considering them, respectively. Therefore, in order to ensure the earthquake resistance of the bridge, the soil properties of the area where the bridge will be built and the wave passage effect of the bedrock must be considered.