Tetracycline hydrochloride (TCH) is an antibiotic whose presence in aqueous environments, even in trace concentrations, is unsafe for living beings. This work reports the fabrication of a promising sonophotocatalyst, graphene nanoribbon-cerium oxide (GNR@CeO₂) heterojunction, for the UV-light driven sonophotocatalytic degradation of TCH. First, GNR@CeO₂ heterojunction was fabricated by the simple sonication assisted 1:1 (w/w) doping of cerium oxide (CeO₂) nanomaterial onto graphene nanoribbons (GNRs) surface. Further, the GNR, CeO₂ and GNR@CeO₂ heterojunctions (20 mg L⁻¹ each) were separately investigated as catalysts in the sonocatalytic (40 kHz ultrasound), photocatalytic (390–400 rpm, UV: 365 nm) and sonophotocatalytic (40 kHz ultrasound, 390–400 rpm, UV: 365 nm) processes for the degradation of TCH (70 mL of 20 mg L⁻¹stock). Among the treatment modes, the GNR, CeO₂ and GNR@CeO₂ heterojunction catalyzed sonophotocatalytic modes recorded the highest TCH removals with 72.9%, 68.3% and 91.2% respectively in 120 min duration. Degradation rates and dynamics obeyed pseudo-first-order kinetics in all the treatment modes. However, GNR@CeO₂ catalyzed sonophotocatalytic mode showed the highest degradation rate with the rate constant k = 0.0290 min⁻¹ and correlation coefficient R² = 0.999, suggesting that the proposed heterojunction acts as effective sonophotocatalyst. The synergy index calculated from the kinetic data also suggests excellent inter-process and inter-catalyst synergy for GNR@CeO₂ catalyzed sonophotocatalytic mode. Further, GNR@CeO₂ heterojunction also showed high reusability and stability in the sonophotocatalytic process, suggesting that the heterojunction coupled with ultrasound and UV-light serve as practically reliable decontamination system for the removal of TCH in water and wastewaters.