The photo-Fenton process is one of the most important advanced oxidation technologies in environmental remediation. However, the poor recovery of catalysts from treated water impedes the commercialization of this process. Herein, we propose a novel approach for the preparation of TiO2-graphene oxide (GO)-Fe3O4 with high photo-Fenton catalytic performance and capability of magnetic recovery. To realize the recovery of the catalysts, the combination of a submerged magnetic separation membrane photocatalytic reactor (SMSMPR) and TiO2-GO-Fe3O4 was applied to degrade the refractory antibiotic organic compounds in aqueous solution. The results indicate that GO can induce better cycle and catalytic performance of the catalysts. Fe3O4 can not only enhance the heterogeneous Fenton degradation of organic compounds but also provide magnetism of the photocatalyst for magnetic separation from treated water. As a result, the TiO2-GO-Fe3O4 composite in the SMSMPR exhibits excellent photo-Fenton catalytic performance and stability for amoxicillin (AMX) degradation. Both back-washing treatment and magnetic separation in the SMSMPR could enhance the photo-Fenton catalytic activity, durability, and separation properties, promoting practical application of this approach for wastewater treatment. Two possible pathways for AMX photodegradation in the SMSMPR were analyzed by means of a Q-TOF LC/MS system, with most of the intermediates finally mineralized to CO2, water and inorganic ions.