This study presents a basin-scale assessment of underwater shipping noise in the Red Sea using a physics-based modeling framework that integrates high-resolution oceanographic fields, satellite-derived Automatic Identification System (AIS) vessel data, and parabolic-equation acoustic propagation modeling. Acoustic transmission was simulated using the Range-dependent Acoustic Model (RAM) forced by temperature and salinity fields from the MIT general circulation model, while ship source levels were estimated from AIS data using an empirical reference spectrum model. Model predictions were evaluated against in situ acoustic measurements collected at six hydrophone sites spanning shallow reef to mesophotic environments during winter and summer deployments. Across the 40–150 Hz band, modeled and measured sound pressure level distributions show good agreement, with median differences typically within ±2 dB at deeper sites and larger, frequency-dependent deviations at shallow locations. Results highlight strong seasonal contrasts in noise levels driven by both vessel traffic patterns and sound speed structure, with winter surface ducting supporting enhanced long-range propagation relative to summer stratification. Basin-wide noise maps reveal elevated sound levels along the main shipping corridor and near port. The validated framework provides essential tools for marine spatial planning and development of mitigation strategies to balance maritime commerce with conservation of the Red Sea’s exceptional marine biodiversity.