Exploring efficient photocatalysts holds significant importance for the prevention and treatment of antibiotic pollution. This research reports a 2D/2D CeO2/BiOCl S-scheme photocatalyst constructed by mesoporous CeO2 and BiOCl nanosheets (NSs). Efficient charge separation and transfer was achieved by the synergistic effect of large-area contact and S-scheme charge transfer mechanism, which significantly enhanced the photocatalytic performance of CeO2/BiOCl. Experimental results demonstrated that the CeO2/BiOCl photocatalyst displayed superior photocatalytic activity to the individual components, which could efficiently eliminate four types of antibiotics, namely tetracycline (TC), chlortetracycline (CTC), doxycycline (DOC), and oxytetracycline (OTC) under UV light irradiation. Particularly, the sample of 0.4CeO2/BiOCl exhibited the highest catalytic efficiency, with a TC degradation rate constant of 0.01524 min−1, which was 1.85 and 22.74 times higher than that of single CeO2 and BiOCl, respectively. Moreover, liquid chromatograph-mass spectrometer (LC-MS) analysis is employed to reveal the degradation pathways of TC. This work offers an insightful idea for the fabrication of novel S-scheme photocatalysts applied in environmental purification.