Capacitive deionization (CDI) has gained a lot of attention as a promising water desalination technology. Among several CDI architectures, multichannel membrane CDI (MC-MCDI) has recently emerged as one of the most innovative systems to enhance the ion removal capacity. The principal feature of MC-MCDI is the independently controllable electrode channels, providing a favorable environment for the electrodes and enhancing the desalination performance. Furthermore, MC-MCDI has been studied in various operational modes, such as concentration gradient, reverse voltage discharging for semi-continuous process, and increase of mass transfer. Furthermore, the system configuration of MC-MCDI has been benchmarked for the extension of the operation voltage and sustainable desalination. Given the increasing interest in MC-MCDI, a comprehensive review is necessary to provide recent research efforts and prospects for further development of MC-MCDI. Therefore, this review actively addresses the major principle and operational features of MC-MCDI along with conventional CDI for a better understanding of the MC-MCDI system. In addition, the innovative applications of MC-MCDI and their notable improvements are also discussed. Finally, this review briefly mentions the major challenges of MC-MCDI as well as proposes future research directions for further development of MC-MCDI as scientific and industrial desalination technologies.