In the arid west, the freshwater supply of many communities is limited, leading to increased interest in tapping brackish water resources. Although reverse osmosis is the most common technology to upgrade saline waters, there is also interest in developing and improving alternative technologies. Here we focus on membrane capacitive deionization (MCDI), which has attracted broad attention as a portable and energy-efficient desalination technology. In this study, a fully coupled two-dimensional MCDI process model capable of capturing transient ion transport and adsorption behaviors was developed to explore the function of the ion-exchange membrane (IEM) and detect MCDI influencing factors via sensitivity analysis. The IEM enhanced desalination by improving the counter-ions’ flux and increased adsorption in electrodes by encouraging retention of ions in electrode macropores. An optimized cycle time was proposed with maximal salt removal efficiency. The usage of the IEM, high applied voltage, and low flow rate were discovered to enhance this maximal salt removal efficiency. IEM properties including water uptake volume fraction, membrane thickness, and fixed charge density had a marginal impact on cycle time and salt removal efficiency within certain limits, while increasing cell length and electrode thickness and decreasing channel thickness and dispersivity significantly improved overall performance.