Introducing stereochemically active lone-pair Sb3+ cations into sulfates, two three-dimensional (3D) antimony-sulfates, Sb4O5SO4 (1) and Sb4O(SO4)(OH)2 (2), were achieved under moderate hydrothermal conditions. Both structures are constructed by tetranuclear-{Sb4}-clusters-based layers and SO4 tetrahedra. However, owing to the different packing patterns of the layers, they display different characteristics: 1 exhibits a centrosymmetric structure while 2 possesses a noncentrosymmetric structure. UV-vis spectra show that they possess wide band gaps. Sb4O(SO4)(OH)2 is nonlinear optical (NLO) active with a second-harmonic generation (SHG) response of ∼1.2 times of KH2PO4, together with the phase-matchable capacity, endowing it a promising UV NLO material. The first-principle calculations were performed to elucidate the structure-property relationships. The results indicate that the lone pair stereoactivity of Sb3+ provides the large contribution to the macroscopic SHG effect.