The visible-light-driven catalyst CeO2/ZnIn2S4 (CeO2/ZIS) was prepared via a hydrothermal method, and its photocatalytic degradation efficiency and mechanism for oxytetracycline (OTC) in water were explored. The morphological characteristics, crystal structure, thermal stability, specific surface area, and optical properties of the catalyst were analyzed by a series of characterization methods. The results showed that the visible light absorption performance of the spherical CeO2/ZIS composed of flakes was significantly improved compared with that of the monomer CeO2. Under the conditions of an initial content of OTC of 30 mg/L, a catalyst dosage of 0.20 g/L, a catalyst dosage of 7.0, and a xenon lamp power of 500 W, the optimal degradation efficiency of OTC by CeO2/ZIS reached 84%. The photocatalytic degradation of OTC by CeO2/ZIS followed a pseudo-first-order kinetic model, with an apparent rate constant of 0.1148 h-1. The exploration of degradation mechanism revealed that the holes (h+) and superoxide radicals (?O_2^-) played major roles during the degradation process of OTC. By combining experimental results with density functional theory (DFT) simulations, a reasonable photocatalytic mechanism for the system was proposed and the stability of the catalyst was verified. This work provides a preparation method for the visible-light-driven catalyst CeO2/ZIS, which can efficiently photocatalytically degrade oxytetracycline in water. The combination of theoretical calculations and experimental results has certain reference value for fully understanding the degradation process of antibiotic pollutants by visible-light-driven catalysts.