Despite efforts and success in lots of noble metal oxides (e.g., RuO 2 and IrO 2 ) electrocatalysts, [5][6][7][8] their high cost, low natural abundance, and scarcity greatly limit their widespread use in large scale. [9] In view of this, it is still highly desirable to design and develop cost-effective high-performance catalysts based on first row transition metal oxides and (oxy) hydroxides to promote OER. [10][11][12][13][14] In recent years, a new group of materials with characteristics of four or five homogenously-distributed principle elements and single phase, namely highentropy (HE) materials are coming into the researchers' sight since composition is the most basic and original factor to determine the bonding, structure, microstructure, and thus properties to a certain extent. [15,16] The HE materials are usually characterized by distinguished effects including sluggish diffusion and cocktail effects from conventional materials. HE materials have been considered as potential candidates to catalyze OER because of their nontrivial electrochemical properties. [17][18][19] HE materials usually possess a highly disordered structure and random distribution of multi ple components because of high configurational entropy. [19] Highly disordered structures can induce high density of defects and even coordinatively unsaturated sites, which mean an abundance of accessible active sites. [20] Random distribution of multiple components will bring great homogeneity, which can result in a synergistic effect to promote interaction between atoms and alter the electronic structure, thereby affecting the intrinsic activity. [21] Furthermore, the entropy stabilization effect can robustly enhance durability of HE materials during electrochemical process. [22,23] Inspired by such unique properties, a few HE materials including fluorides, oxides, and alloys have been developed and utilized for OER process. Wang et al. [17] synthesized HE perovskite fluorides and verified with excellent OER performance (a low overpotential of 314 mV at a current density of 10 mA cm −2 ). In addition, Wang et al. [18] prepare HE oxides (i.e., (Co, Cu, Fe, Mn, Ni) 3 O 4 oxides) via a solvothermal method and achieved a current density of 10 mA cm −2 at 1.58 V in 1 m KOH. Meanwhile, Dai et al. [16] reported MnFeCoNi HE alloys for OER with a low overpotential of 302 mV at a current density High-entropy materials are new-generation electrocatalysts for water splitting due to their excellent reactivity and highly tailorable electrochemical properties. Herein, a powerful top-level design strategy is reported to guide and design advanced high-entropy electrocatalysts by establishing reaction models (e.g., reaction energy barrier, conductivity, adsorption geometries for intermediates, and rate-determining step) to predict performance with the help of density functional theory (DFT) calculations. Accordingly, novel high-entropy Co-Cu-Fe-Mo (oxy)hydroxide electrocatalysts are fabricated by a new low-temperature electrochemical reconstruction method and the...