Freak wave is an extreme sea state with unexpected and huge wave height, which becomes a potential risk for lay barge and offshore pipeline during deepwater installation. In order to investigate the dynamic responses of deepwater S-lay pipeline induced by freak waves, this study developed a comprehensive numerical model with the particular consideration of the freak wave effect. An enhanced superposition method of combined transient wave trains and random wave trains was presented, and a series of freak wave trains were generated. The induced pipelay vessel motions were simulated by the use of displacement response amplitude operators (RAOs). The pipe–stinger roller interactions in the overbend and the cyclic contacts between the pipeline and seabed soil in the touchdown zone (TDZ) were fully taken into consideration. The developed S-lay model was subsequently utilized to calculate the dynamic responses of the pipelay vessel and offshore pipeline under random waves and freak waves for a comparison. The results illustrated the remarkable influence of freak waves on the systematic behaviors of deepwater S-laying pipeline, which offer a significant theoretical basis for the pipe structure design and pipelay operation safety.