Overhead pipeline is a typical, long-flexible structure. Ground motions of different support are distinct due to the seismic wave propagation, seismic wave attenuation, and soil nonuniformity. To analyze the effect of differential inputs on the seismic response of overhead pipelines, seismic responses under coherence function input, traveling wave input, and uniform input were simulated and compared. An overhead pipeline model was established using the finite element software Automatic Dynamic Incremental Nonlinear Analysis (ADINA), and artificial seismic waves with coherence effects were compiled by MATLAB. Results showed that:(1) As the apparent wave velocity increased, the axial strain of the pipe decreased, which was close to the case of a consistent excitation; (2) maximum axial strain of pipelines having the same coherence function model was different with and without the consideration of site effect; and (3) for different coherence function models, the maximum axial strain of the pipeline was also distinct. It is concluded that if the site is uniform and the pipeline is short, the traveling wave method can be used for seismic input, the coherence method should be used for seismic response analysis of long flexible pipelines, and the site effect should be considered simultaneously for long flexible pipelines over an uneven site.