Electrochemical decomplexation is a common technique that is widely used in industrial wastewater treatment. Although much research has been conducted to improve the decomplexation efficiency of metal–organic complexes [e.g., Ni-ethylenediaminetetraacetic acid (EDTA)], the effects of the fundamental electrochemical reactor configurations in this technology are often underestimated. This research provides insights into the role of the reactor configuration in electrochemical decomplexation of Ni-EDTA through experiments and simulations. Degradation experiments were conducted at the same current density and flow rate in flow-by (FB) and flow-through (FT) electrochemical reactor configurations. The results show that the FT reactor gives a better removal rate (FB: 35%, FT: 46%) and that its energy consumption is half that of the FB reactor [approximately 207.78 (kW·h)/(kg Ni) less]. Experiments show that the stagnant and back-mixing zones for the FT configuration (D_z ​= ​0.062) are smaller than those for the FB configuration (D_z ​= ​0.205). This promotes mass transport in the reaction environment and decreases problems with the reactor performance. Computational fluid dynamics simulations showed that the velocity and potential distributions were both more even for the FT than for the FB configuration. This increases uniformity of mass transport and the current density distribution, produces less ohmic resistance, and greatly improves energy saving. These experimental and simulation results will enable Ni-EDTA electrochemical decomplexation to be achieved with low energy consumption and high efficiency by using appropriate reactor configurations.