Low-valent vanadium(III) with d² electronic configuration, which can generate significant magnetic anisotropy, is highly desirable for the construction of high-performance molecule-based magnetic materials. Such lightweight and flexible magnetic materials cannot be realized by conventional inorganic or alloy-based permanent magnets. However, owing to the facile oxidation of vanadium(III), the synthesis of stable complexes containing highly reduced V(III) or mixed low-valent V(III,IV) centers remains extremely challenging. To date, only a limited number of V(III) or V(III,IV)-based coordination complexes or clusters have been isolated, most of which possess a nuclearity lower than eighteen. Herein, we report the self-assembly of a giant V(III,IV) cluster, namely {V^III₂₀V^IV₂O₈(OH)₈(CH₃COO)₂₄(CH₃CH₂O)₂₀}·5CH₃CH₂OH (V₂₂), from a trinuclear vanadium precursor. The resulting large V₂₂ cyclic coordination cluster exhibits an unusual small triplet ground spin state, which arises from antiferromagnetic exchange interactions. Moreover, this cluster system is detectable by electron paramagnetic resonance (EPR) spectroscopy and displays prominent quantum characteristics.