The processes governing the seasonal evolution of the oceanic mixed layer temperature (MLT) and salinity (MLS) in the Red Sea (RS) are analyzed using the outputs of a high-resolution (1/100°) ocean general circulation model for 2001 to 2015, forced by a high-resolution (5 km) regional atmospheric reanalysis. We quantify the roles of atmospheric forcing and the advective, diffusive, and entrainment processes in the seasonal variability of mixed layer (ML) properties by analyzing the closed and complete potential temperature and salinity budgets integrated over the ML depth. The seasonal evolution of the ML density is predominantly driven by the MLT, which is dominated by the air–sea heat exchange. The seasonal evolution of MLS is predominantly driven by the advection of fresher waters from the Gulf of Aden, whereas atmospheric forcing governs its gradual increase along the basin. The spatial distribution of strong mesoscale circulation and semipermanent eddies is imprinted on all processes, whereas advective fluxes tend to follow meandering currents around the periphery of mesoscale eddies. Entrainment processes affect the ML density through the reemergence of heat and salt stored below the ML. Entrainment is especially important in the northern parts of the RS, where increased salinity preconditions the upper layers for ML deepening and denser water formation.