This paper analyzes the role of the conducting layer substrates (Cu and fluorine-doped tin oxide (FTO)) on grown copper oxide (CuO) in order to improve the performance of catalytic bacterial inactivation. Growth of CuO onto Cu substrate was via thermal oxidation of Cu whereas hydrothermal method was employed for CuO growth onto FTO. The surface morphology of CuO varied with respect to the substrates choice and epitaxy, developing particulated thin film and thin film consisting vertically aligned nanorods on Cu and FTO, respectively. Photo- and electro- based reactions were carried out to understand the effect of light, bias, bias-catalyst and light-bias-catalyst combinations, respectively, for the fast killing of E. coli. The experimental results showed a striking improvement in photoelectrocatalytic inactivation of E. coli using plain fabricated copper oxide substrate. The choice of conducting substrate material plays a crucial role in terms of both morphology controlled CuO growth under different facile methods and also governs the electron transfer efficiency to achieve an improved catalytic efficiency. The reaction mechanism was discussed by deriving an appropriate detailed model which is able to predict the experimental data in all the cases. This study gives an insight on energy saving and less carbon footprint approach for bacterial killing in a short interval. © 2017 Elsevier B.V.