Extreme loads are often a key cost driver for wave energy converters (WECs). As an alternative to exhaustive Monte Carlo or long-term simulations, the most likely extreme response (MLER) method allows mid- and high-fidelity simulations to be used more efficiently in evaluating WEC response to events at the edges of the design envelope, and is therefore applicable to system design analysis. The study discussed in this paper applies the MLER method to investigate the maximum heave, pitch, and surge force of a point absorber WEC. Most likely extreme waves were obtained from a set of wave statistics data based on spectral analysis and the response amplitude operators (RAOs) of the floating body; the RAOs were computed from a simple radiation-and-diffraction-theory-based numerical model. A weakly nonlinear numerical method and a computational fluid dynamics (CFD) method were then applied to compute the short-term response to the MLER wave. Effects of nonlinear wave and floating body interaction on the WEC under the anticipated 100-year waves were examined by comparing the results from the linearly superimposed RAOs, the weakly nonlinear model, and CFD simulations. Overall, the MLER method was successfully applied. In particular, when coupled to a high-fidelity CFD analysis, the nonlinear fluid dynamics can be readily captured.