In this paper, we investigated sonophotocatalytic degradation of sulfamethoxazole (SUX) antibiotic in pharmaceutical wastewaters by employing a ternary heterostructure catalyst composed of MgOand ZnO nanoparticles anchored on graphene nanosheets (MZG) under UV-A (LED) and US irradiations as a novel study. Synthesis of MZG was performed via multi-step hydrothermal-assisted method and characterizedby employing XRD, FT-IR, FESEM, BET, EIS, DRS, EDS, TEM, EDX, and TGA techniques. By introduction of ZnO and graphene, photocatalytic activity of MgO was enhanced in both UV and visible regions. A good catalytic potential and significant synergistic effect was obtained for ternary system (MZG/LED/US) compared to binary and single processes. After 120 min of sonophotocatalytic treatment, complete degradation of SUX (55 mg/L) can be attained at MZG: 0.8 g/L, pH: 9.0, LED power: 90 W and US power: 250 W. Kinetic studies revealed that sonophotocatalytic degradation process followed the pseudo first-order kinetic model. HO species were detected as dominant oxidative free radicals which contributed in SUX degradation process. A comprehensive possible mechanism was proposed for photocatalysis and sonocatalysis processes involved in MZG/LED/US system in detail. The nanocomposite was reused for six successive cycles with maximum 9.8% drop in degradation efficiency. An efficient improvement was achieved in the biodegradability of real pharmaceutical wastewater after treatment by MZG/LED/US with 94% and 81% removal of COD and TOC, respectively. To conclude, combining MZG, LED and US waves can be utilized as a novel and efficient strategy to treat real pharmaceutical wastewaters in practical applications, owing to high performance in degradation/mineralization, excellent reusability potential and high activity in sonolysis and photolysis systems.