This study experimentally and numerically investigated interactions between solitary waves and the perforated caisson breakwaters. By caisson, we mean a sealed chamber filled with sand and rocks inside, and it is a common structure used for the construction of vertical breakwater. In the laboratory, the solitary waves with larger relative wave heights were well generated based on the “collapsing water column” technique and successfully acted on the perforated caisson models. Using the volume of fluid method and the k–ε model, combined with the ideal gas equation at a constant temperature, the wave transformation and vortex evolution in the vicinity of the perforated caisson breakwaters were simulated. A reasonable agreement was observed between the numerical and the experimental results. By comparing with the non-perforated caissons, the perforated caissons effectively reduced the reflected and transmitted wave heights, and the occurrence of the reflected waves was found to be delayed due to the existence of the wave chamber. Based on the numerical results, distributions of the fluid velocity and turbulence kinetic energy (TKE) near the perforated caissons were examined. The wave dissipation mechanism of perforated caisson under the solitary wave was different from that under the periodic wave. The results showed that vortices and TKE were mainly concentrated near the perforated front wall. The incident wave energy was dissipated in the generating vortices formed by fluids jetting through perforations. Additionally, variations of the wave reflection, transmission, dissipation coefficients, and wave overtopping volumes were investigated against different relative crest freeboards, relative wave chamber widths, caisson porosities, and relative wave heights under the solitary waves. Valuable results were presented for practical engineering applications.