In this study, redox-flow battery desalination (FBD) with a four-channel cell architecture was utilized for electrochemical desalination at different salinity levels. Herein, continuous desalination without a discharge step was achieved by simultaneous generation of desalted and brine streams in the diluted and concentrated chambers, while the ferri-/ferrocyanide redox couple was independently recirculated between the anode and cathode chambers. Notably, a relatively low constant voltage of 0.2 V successfully drove redox reactions for ion motion. The salt removal rate was enhanced by increasing the applied voltage but at the cost of higher energy consumption. Employing a higher concentration of ferri-/ferrocyanide (i.e., 100 mM) provided faster reaction kinetics and charge transfer in the FBD chambers. By treating NaCl solutions with concentrations in the range 3000–35,000 mg/L at 0.2 V, we demonstrated that the average salt removal rate increased from 14.7 to 96.2 μg/min-cm2. The molar energy consumption increased slightly from 18.5 to 20.6 kJ/mole, which was associated with a high charge efficiency >93.8%. This feature indicates the possible utility of FBD for desalting solutions with high salinity levels up to that of seawater. As demonstrated, FBD delivered >90% salt removal for real seawater desalination with an energy consumption of 3.34 kWh/m3.