The recirculatory microbial desalination cell–microbial electrolysis cell (MDC–MEC) coupled system is a novel technology that generates power, treats wastewater, and supports desalination through eco-friendly processes. This study focuses on the simultaneous efficient removal of Fe²⁺ and Pb²⁺ in the MEC and ammonium ions in the MDC. It also evaluates the performances of dual-chambered MEC (DCMEC) and single-chambered MEC (SCMEC), coupled with MDC with Ferricyanide as catholyte (MDCF) in heavy metals (Pb²⁺ and Fe²⁺) removal, in addition to the production of voltage, current, and power within a 48-h cycle. The SCMEC has a higher Pb²⁺ (74.61%) and Fe²⁺ (85.05%) removal efficiency during the 48-h cycle than the DCMEC due to the simultaneous use of microbial biosorption and the cathodic reduction potential. The DCMEC had a higher current density of 753.62 mAm⁻² than that of SCMEC, i.e., 463.77 mAm⁻², which influences higher desalination in the MDCF than in the SCMEC within the 48-h cycle. The MDCF produces a higher voltage (627 mV) than Control 1, MDC (505 mV), as a power source to the two MECs. Stable electrolytes’ pH and conductivities provide a conducive operation of the coupled system. This study lays a solid background for the type of MDC–MEC coupled systems needed for industrial scale-up.