Different modeling methods and potential flow methods have substantial influences on the prediction results of wave loads and hydroelastic responses of ships traveling in waves, so it is of great importance to carry out uncertainty analyses for relevant aspects. For a very large bulk carrier, the 1D Euler–Bernoulli beam and 3D FEM are used to build the dry structure model, and 3D methods in the frequency domain and time domain are used to predict the wave loads. The influences and uncertainties of the structure modeling method on the hydroelastic response and wave load are assessed, which indicates that the 1D Euler–Bernoulli beam model overestimates the resonant frequencies. Furthermore, the hydroelastic responses and wave loads are analyzed using three-dimensional methods in the frequency domain and time domain for a 205,000 DWT bulk carrier, a 500,000 DWT ore carrier and a 156,800 m3 LNG carrier. Furthermore, a comparison is conducted between the numerical prediction results and experimental data measured from the see-keeping basin; meanwhile, the error principles of the numerical analysis are investigated, which infers that the vertical bending moment and horizontal bending moment have smaller numerical prediction errors, while the torsional moment has the largest error.