We present a novel multichannel membrane flow-stream capacitive deionization (MC-MCDI) concept with two flow streams to control the environment around the electrodes and a middle channel for water desalination. The introduction of side channels to our new cell design allows operation in a highly saline environment, while the feed water stream in the middle channel (conventional CDI channel) is separated from the electrodes with anion- and cation-exchange membranes. At a high salinity gradient between side (1000 mm) and middle (5 mm) channels, MC-MCDI exhibited an unprecedented salt-adsorption capacity (SAC) of 56 mg g−1 in the middle channel with charge efficiency close to unity and low energy consumption. This excellent performance corresponds to a fourfold increase in desalination performance compared to the state-of-the-art in a conventional CDI cell. The enhancement originates from the enhanced specific capacitance in high-molar saline media in agreement with the Gouy–Chapman–Stern theory and from a double-ion desorption/adsorption process of MC-MCDI through voltage operation from −1.2 to +1.2 V.