It is reported in the literature that Electrodialysis Desalination (ED) is the most efficient for groundwater (<7 ppt), while Reverse Osmosis (RO) is for higher salinity (8–50 ppt). Thus, the present paper proposes a novel arrangement of ED-RO for brackish water desalination. ED is used first for brackish water desalination, while RO treats the highly concentrated outlet of the ED part. Energy consumption, water production, recovery ratio, and water cost are the performance indices discussed in this paper. These are presented against the influential input parameters, which are selected based on a sensitivity analysis. The results show that the new system is economically feasible for inlet salinity of 2.5–7.8 ppt. Standalone RO could be better for salinity more than eight (8) ppt, and standalone ED is better for a source salinity of less than two (2) ppt. Energy consumption results emphasize that the ED-RO integration is the most energy-effective for the feed salinity of < 9.5 ppt. The net recovery ratio for the hybrid ED-RO plant is 87.5% when ED and RO plants operate at a recovery ratio of 75% and 50%, respectively. For typical conditions and brackish water salinity of 5 ppt, ED-RO shows an outstanding performance of 0.731 kWh/m3 for energy consumption and 0.370 $/m3 for water cost. These values are better than those of standalone RO and ED plants.