The oxygen evolution reaction is a key reaction in rechargeable metal air battery. Nickel oxide (NiO) nanoparticles are a potential low-cost oxygen evolution reaction (OER) electrocatalyst, and its catalytic activity and stability are still to be further improved. The construction of interfacial catalysts can improve their electrocatalytic activity. In this work, we report that nickel oxide (NiO) nanoclusters supported on chromium oxide (Cr2O3) nanosheets form a novel NiO–Cr2O3 heterostructure as an effective electrocatalyst for OER. Compared with pristine NiO and Cr2O3, NiO–Cr2O3 exhibits higher OER activity with smaller overpotential of 270 mV and lower Tafel slope of 30 mVdec−1, as well as durability under alkaline conditions. The X-ray photoelectron spectroscopy, In-situ Raman spectra and theoretical calculations reveal a source of high catalytic activity of NiO–Cr2O3. The results show that the activity site is located at Cr–Ni site of the NiO–Cr2O3. Due to the obvious charge transfer between Cr and Ni atoms at the interface, the change of Ni and Cr electronic structure reduces the adsorption energy of oxygen species and increases their catalytic activity. This work constructs a new Cr–Ni interface coupling method through NiO–Cr2O3 heterostructure, which provides a new strategy for designing new efficient and inexpensive OER catalysts.