The formation of chlorinated by-products in the treatment of chloride-laden water/wastewater by advanced oxidation processes (AOPs) has become a severe challenge to their environmentally benign application. Herein, we propose an efficient and safe alternative, i.e., flow-through anodic oxidation (FTAO) system based on the nonradical direct electron transfer (DET) process at low voltage. By controlling the anode potential below the threshold for chlorine evolution at the anode, this system achieved zero formation of inorganic and organic chlorinated byproducts whilst significantly eliminated the biotoxicity of the parent micropollutant. Meanwhile, due to the nonradical direct oxidation mechanism, the voltage-confined FTAO system attained high efficiency and selectivity for the micropollutant removal from a complex matrix containing naturally co-existing anions and organic matter. The feasibility of FTAO applications was further evaluated by removing various pollutants (including antibiotics and phenols) from actual municipal effluent and surface water. More than 96 % percentage removal was achieved at extremely low energy consumption (0.003–0.017 kWh m−3). In summary, our results provide insight into the development of novel electrochemical technologies free from secondary pollution towards environmental remediation applications and beyond.