In this research, Fe-doped BiOCl nanosheets were successfully synthesized through controlled hydrothermal method and applied in the degradation of levofloxacin (LVX) by sulfate radical-based photo-Fenton process. The conduction band of Fe-doped BiOCl was calculated as 2.77 eV compared to BiOCl (3.24 eV), and showed remarkable visible-LED-light driven photocatalytic activity with the expanded visible light absorption. Certain parameters were studied, with the addition persulfate (1 mM) and catalyst dosage (0.5 g L−1) at natural pH, the LVX reached over 95% degradation efficiency in 60 min during at least five successive experiments which displayed excellent catalytic activity and stability. LVX degradation was confirmed to depend on the formation of free reactive oxidant species through radical scavenger reagents and EPR analysis. On the basis of the experimental results and density functional theory calculations, the role of photocatalytic degradation mechanism of LVX degradation by the Fe-BiOCl sample was investigated. Moreover, the LVX degradation pathway was induced according to the intermediates detected by LC-MS. The results of this research demonstrated the good feasibility of Fe-doped BiOCl nanosheets which would enhance the utilization of photocatalysts under visible light irradiation.