This numerical study provides insight into the mechanism of noise generation by a cavitating flow in the wake of a marine propeller under realistic operating conditions, which poses a significant threat to marine ecosystems. We examined a full-scale vessel with an entire hull and an isolated model-scale marine propeller (INSEAN E779A) with a maneuverable rudder under various highly turbulent inflow conditions that strongly affect the spectral characteristics of the radiated noise. Insight into the acoustic behavior was gained by employing a combination of the large eddy simulation (LES) treatment of turbulence and the Schnerr–Sauer volume of fluid cavitation model. The hydrodynamic solution was coupled with the Ffowcs Williams-Hawkings (FW-H) strategy for noise and vibration identification. We focused on the interactions between the characteristic cavitation patterns of marine propellers (sheet, tip, and hub cavities) and the dominant structures of the turbulent wake (tip, root, trailing edge, and hub vortices, as well as the distributed small-scale vorticity). The small-scale topological structures in the swirling wake of a propeller directly manifest in the radiated sound level and affect the intensity of multiple frequency ranges. Quantitative analysis of thrust, pressure fluctuations, and sound pressure levels (SPLs) demonstrates significant effects of blade loading, wake distribution, and cavitation development. The peak and average SPL distributions obtained through LES show lower dominant and higher average frequencies compared to those obtained by the FW-H method. The overall SPL obtained by LES were higher than those calculated using the FW-H acoustic analogy at all microphone locations. The overall noise was dominated by the low-frequency broadband noise, attributed to energetic helical vortices, and narrow-band peaks in the medium-high frequency range that originated from other sources, like cavitation structures.