This work focuses on the degradation of the hazardous azo dye Naphthol Blue Black (NBB) utilizing an innovative approach combining electro-Fenton (EF), ultra-violet (UV), and ultra-sound (US) processes while varying the operating parameters (concentration of iron and dye, pH, current intensity). Under the optimum experimental conditions, an excellent degradation efficiency of the NBB dye is achieved after 60 min, i.e., 98%, 95%, and 65% for EF, UV, and US processes, respectively. The addition of persulfate significantly improves the efficiency and accelerates the kinetics of the NBB degradation. Combining all processes assisted with persulfate achieved 99% NBB degradation within a very short contact time of 2 min and 98% reduction in COD after 55 min. The as-obtained outstanding performance associated with the synergistic effects of EF/US/UV alongside the addition of persulfate can be adopted to degrade other hazardous substances.