Chloride ions (Cl–) are ubiquitous in reclaimed water and can cause a variety of problems in water reuse systems. Flow electrode capacitive deionization (FCDI) shows good prospects for energy-efficient desalination, but its applications were still hindered due to the low ion removal efficiency resulting from the limited conductivity of flow electrodes composed of carbon materials and aqueous electrolytes. Herein, this study introduced redox mediator Fe2+/Fe3+ ox/red in flow electrodes resulting in higher chloride ions removal efficiency (80.57%) and charge efficiency (85.22%) compared to the FCDI system without Fe2+/Fe3+ (49.64 and 53.37%, respectively). An asymmetric Fe2+/Fe3+-mediated FCDI system that could avoid leakage of the Fe2+/Fe3+ was also proposed. It was found that the high performance was due to Fe2+/Fe3+ ox/red promoting electrodialysis and capacitive deionization. The long-term operation was conducted, and the system showed good stability without the formation of iron hydroxide precipitation. Under optimized conditions, the high removal efficiency (88.28%) could be achieved in treating the actual reclaimed water, implying the practical applicability of the Fe2+/Fe3+-mediated FCDI system. The insights gained in this work are expected to facilitate the further development of a useful flow electrode capacitive deionization technology.