The presence of antibiotics in waste and drinking water is causing increasing concern around the world, thereby an advanced sustainable technology needs to be developed to eliminate the antibiotics from water resources. Hence, an efficient spinning disc photoreactor (SDPR) equipped with visible light-activated Ag/Ag2O/TiO2 heterostructure thin film photocatalyst was assessed for the degradation of amoxicillin (AMX) as a typical antibiotic. The surface morphology, optoelectronic and structural features of Ag/Ag2O/TiO2 heterojunction were characterized by TEM, BET, mott Schottky, FESEM, EDS, AFM, XRD, UV–Vis-DRS, and contact angle measurements. Results confirm that Ag and Ag2O have a significant effect on the photocharge carrier separation and transfer of the as-developed photocatalyst system. The operative variables including illumination time, rotational speed, solution flow rate, aeration rate, pH, and initial AMX concentration were optimized by CCD. The results displayed the maximum AMX photodegradation (97.91%) could be achieved at optimal conditions involving illumination time of 80 min, a rotational speed of 225 rpm, the solution flow rate of 0.6 L/min, aeration rate of 20 L/min, pH = 6, and initial AMX concentration of 20 mg/L. Interestingly, more than 79% COD and 64% TOC were removed under optimum conditions during 80 min illumination time, respectively. Active species tests confirmed the dominant role of ·OH and ·O2− in AMX degradation. finally, the XRD pattern confirmed that the reusability assessments of the heterojunction film could successfully retain its stability for six consecutive photocatalytic degradation runs. This work demonstrates the feasibility of utilizing visible-light-driven thin-film photocatalysts in spinning disc photoreactors in treating the tenacious antibiotic pollutants.