The high-pressure Raman spectra in the low-wavenumber region (50–1200 cm−1) and the hydroxyl stretching vibration region (2600–3800 cm−1) of fluorapophyllite-(K) were collected in the interval of 0.0–50.7 GPa. Experimental results show that fluorapophyllite-(K) undergoes a crystalline-crystalline phase transition from a tetragonal structure (P4/mnc) to an orthorhombic structure (Pnnm) and then amorphization under high pressure conditions. Discontinuous changes in Raman peaks in the hydroxyl vibration region (2600–3800 cm−1) and the low-wavenumber region (50–1200 cm−1) occur at different onset pressures, suggesting that the destabilization of sub-lattices in fluorapophyllite-(K) under high pressure is not synchronous; the weak interlayer H2O structural units are more prone to destabilization at lower pressures than the rigid SiO4 tetrahedral layer units. Therefore, H2O groups in fluorapophyllite-(K) serve as sensitive local probes during the pressure-induced phase transition and amorphization.