Rationally developing electrocatalysts toward oxygen evolution reaction (OER) is of fundamental concern for enhancing water electrolysis efficiency. Nickel based selenides are deemed as promising OER catalysts thanks to their good electrical conductivity and easy regulation. In this work, different amount of Fe was incorporated into NiSe2 nanoparticles through a facile one-pot solvothermal approach, the impact of which was investigated detailedly and deeply. Modifying NiSe2 with a small content of Fe can enlarge electrochemical active surface area and regulate electronic structure and valence state of active center. Moreover, density functional theory (DFT) calculations manifest Fe incorporation can increase Bader charge of Ni site, improve electron delocalization and electronic conductivity, and tune the interaction between catalyst and OH*, therefore significantly enhancing OER activity. The increase of surface Fe content within a definite scope can cause gradual decrease of band gap, and increase of OH– adsorption strength. The intrinsic activity follows the order of NiSe2 < Fe0.17Ni0.83Se2 < Fe0.33Ni0.67Se2 ≈ Fe0.5Ni0.5Se2. Accordingly, the as-prepared Fe-NiSe2-25 with surface Ni/Fe ratio of 2:1 delivers markedly boosted OER activity and remarkable stability, demanding a low overpotential of 250 mV to drive 10 mA cm−2. Moreover, rechargeable liquid and solid Zn-air batteries and water electrolysis tests manifest the potential real application of Fe-NiSe2-25 in energy conversion devices. This work can provide a profound and revealing insight into the impact of iron incorporation on electrochemical properties, and inspire more research to explore other types of Fe-doped transition metal-based compounds by engineering the band gap and electronic structure.