Highly efficient decontamination of naturally occurring As(III) from aqueous media remains a rigorous task for public health and ecosystem protection. As its increasingly acute toxicity and mobile characteristics than those of As(V), it is imperative to exploit a technique for the simultaneous removal and detoxication of As(III). Herein, a novel strategy involving outer and inner structural engineering of an amorphous FeMn-MOF-74 adsorbent was developed via a facile temperature-controlled crystallization method, which integrated the inner amorphous structure with low-coordinated active centers and the outer optimized metal atomic ratio with homogeneous adsorption/oxidation sites for generating the synergistic effects of As(III) removal. An appropriate Fe/Mn ratio (∼1.96) with optimized temperature (denoted as aFMM-120) endows the synergic effect of iron and high-valence manganese nodes in the framework with the highest experimental adsorption capacity of 161.6 mg g−1 among MOF-based arsenic adsorbents. Detailed characterizations through X-ray photoelectron spectroscopy and Fourier-transform infrared spectroscopy demonstrated the redox behavior of Mn species and surface coordination of oxygen molecules in FeO clusters toward As(III). All these results imply that amorphous aFMM-120 is an effective adsorptive oxidation material for efficient arsenic-contaminated water remediation.