FeSbO4 exhibits an extraordinarily high electrical resistance of ∼650 GΩ at pressures near 7 GPa at room temperature. Pressure-induced electrical transport measurements reveal a large resistance increase of 106 compared to ambient pressure. This is the result of a very strong Coulomb repulsion between localized iron 3d-electrons caused by an abrupt shortening of the axial Fe(3d)/Sb(5s)–O(2p) σ-bonds in the Fe/SbO6 octahedra as verified by in situ X-ray diffraction (XRD) study. Subsequent and concomitant strengthening of Sb–O and weakening of Fe–O bonds drive FeSbO4 into a Mott insulating state. Upon increasing pressure to 13 GPa, XRD and optical absorption spectroscopy further confirm a first-order phase transition from a tetragonal insulator with Fe3+ in a high spin state to an orthorhombic semiconductor with Fe3+ in a low spin state without any metallization. Powder diffraction and transmission electron microscope images reveal that the recovered sample after pressure release preserves the high-pressure orthorhombic structure albeit with Fe3+ in a high spin state and maintains its high resistance. The behavior at moderate pressures might be useful for potential applications in electronic switches, piezoresistive sensors, and other electronic devices.