In order to solve the increasingly serious environmental pollution and energy crisis as soon as possible, engineering of two-dimensional/two-dimensional (2D/2D) S-scheme heterojunctions is in the spotlight. Herein, two-dimensional/two-dimensional (2D/2D) S-scheme Fe2O3/Bi2MoO6was designed and fabricated through a facile hydrothermal strategy, which constructed an advanced photocatalytic-Fenton coupling system. With the assistance of a low concentration of H2O2, the 2D/2D Fe2O3/Bi2MoO6with an Fe2O3weight ratio of 0.5% displayed significantly enhanced photo-Fenton catalytic activity toward tetracycline, which was 3.2 and 2.0 times that of Fe2O3and Bi2MoO6, respectively. The markedly enhanced photo-Fenton catalytic activity was attributed to the large surface area and efficient charge transfer of 2D/2D S-scheme Fe2O3/Bi2MoO6, as well as the photo-Fenton system constructed by H2O2and continuous Fe3+/Fe2+conversion under visible light irradiation. According to the active species trapping experiments and photoluminescence spectra, a novel 2D/2D S-scheme charge transfer mechanism of Fe2O3/Bi2MoO6was reasonably proposed. Fe2O3/Bi2MoO6composites displayed a broad application prospect due to their recyclability demonstrated by the cycling experiments. This work provides strong evidence that 2D/2D S-scheme Fe2O3/Bi2MoO6heterostructures are promising candidates for the photo-Fenton treatment of antibiotics.