The growth of layered double hydroxide (LDH) structures on transition-metal substrates shows great potential for generating highly effective and low-cost water electrolysis catalysts. Herein, nanochains of hollow nickel mesospheres (hNi) synthesized using a template-free reflux method were utilized to develop NiFe-OH. Subsequently, the acid-treated hNi (hNiH) induced the formation of a three-dimensional hierarchical hNiH@NiFe-OH structure possessing an LDH framework. Its growth was regulated by the Fe(II) ions and an optimum chloride ion concentration as determined via the corrosion mechanism. The electrocatalytic activity of the hNiH@NiFe-OH catalyst for the oxygen evolution reaction (OER) was superior to those of references such as hNi, Fe nanowires, hNi@NiFe, and commercial Ir/C catalysts as confirmed by its lowest overpotential value (288 mV at 10 mA cm −2 ) and efficient catalytic kinetics indicated by a Tafel slope of 37 mV dec −1 . Furthermore, this catalyst demonstrated remarkable stability during the OER process, with the overpotential at 10 mA cm −2 showing a marginal increase (16 mV) over 10,000 cycles, whereas a 38 mV increase was observed for Ir/C. These findings successfully demonstrate that the depassivation-assisted in situ NiFe-OH formation using hNiH nanochains is a promising approach for developing highly efficient OER catalysts.