Heterointerface engineering enhances catalytic active centers and charge transfer capabilities to increase oxygen evolution reaction (OER) and hydrogen evolution reaction (HER) kinetics. In this study, a novel heterostructure of manganese cobalt sulfide-molybdenum disulfide on nickel foam (MnCo2S4-MoS2/NF) was synthesized via a two-step hydrothermal process. The nanowire-shaped MnCo2S4-MoS2 on NF displayed accelerated charge transfer ability and multiple integrated active sites. When tested in one molar (1 M) potassium hydroxide (KOH) electrolyte, it furnished low overpotentials of 105 and 171 mV for the HER and 220 and 300 mV for the OER at the current densities of 20 and 50 mA cm−2, respectively. An electrolyzer based on MnCo2S4-MoS2/NF required low operating potentials of 1.41 and 1.49 V to yield the current densities of 10 and 20 mA cm−2, respectively, surpassing commercial and previously reported catalysts. Density functional theory (DFT) analysis revealed that the MnCo2S4-MoS2 heterostructure possesses the optimal adsorption free energies for the reactants, an extended electroactive surface area, good charge transfer ability, and reasonable density of electronic states close to the Fermi level, all of which contribute to the high activity of catalyst. Thus, heterointerface engineering is a promising strategy for creating efficient catalysts for overall water splitting.