This paper considers hub-depth impacts on mechanical loads for a tidal turbine operating in realistic coupled wave–current sea states. A novel medium-fidelity actuator-line CFD model for simulating tidal turbine non-steady hydrodynamic rotor load responses in the presence of turbulence, shear, and surface waves is developed. The model is validated using tank testing data from a lab-scale turbine. The validated model is then upscaled, to a power rating of 1.5 MW, and simulated in realistic wave–current conditions consistent with those of the MeyGen site. Mean torque and thrust are found to increase with turbine hub height, and the presence of waves is shown to increase mean torque and thrust values by up to 22% and 11%, respectively. The effect on standard deviations and maximum values for these variables is more pronounced, with increases of up to 2500% and 1700% in signal standard deviations, and up to 80% and 30% in maximum values for torque and thrust, respectively. The presence of longer period waves is also shown to reduce mean torque levels, while the corresponding standard deviations and maximum values remained relatively unchanged. In such circumstances, the turbine is operating with an undesirable combination of low-power and high-fatigue. Tidal turbine hub loading characteristics and sensitivities, in the context of the operational loads which subsequently enter the drivetrain and turbine support structure, are also analysed. The magnitude of out-of-plane rotor moments are found to increase with the hub height and wave height. Complex flow interactions are shown to play an important role in this context, leading to what is termed “wave-driven moment-type dominance” effects. Overall, both the rotor location and wave composition are found to significantly impact the turbine’s rotor mechanical load response.