Visible light-driven photo-Fenton-like technology is a promising advanced oxidation process for water remediation, while the construction of effective synergetic system remains a great challenge. Herein, iron hydroxide oxide (α-FeOOH) with controllable oxygen vacancy defects were engineered on reduced graphene oxide (rGO) nanosheets (named as OVs-FeOOH/rGO) through an in-situ redox method for boosting visible light-driven photo-Fenton-like oxidation. By adjusting the pH environment to modulate the redox reaction kinetics between graphene oxide (GO) and ferrous salt precursors, the oxygen vacancy concentration in α-FeOOH could be precisely controlled. With optimized oxygen vacancy defects obtained at pH 5, the OVs-FeOOH/rGO displayed superior photo-Fenton-like performance for Rhodamine B degradation (99% within 40 mins, rate constant of 0.2278 mg−1 L min−1) with low H2O2 dosage (5 mM), standing out among the reported photo-Fenton-like catalysts. The catalyst also showed excellent reusability, general applicability, and tolerance ability of realistic environmental conditions, which demonstrates great potential for practical applications. The results reveal that moderate oxygen vacancy defects can not only strengthen absorption of visible light and organic pollutants, but also promote the charge transfer to simultaneously accelerate the photogenerated electron-hole separation and Fe(III)/Fe(II) Fenton cycle, leading to the remarkable photo-Fenton-like oxidation performance. This work sheds light on the controllable synthesis and mechanism of oxygen vacancy defects to develop efficient photo-Fenton-like catalysts for wastewater treatment.