We report the high-pressure response of guanidinium methanesulfonate (C(NH2)(3)(+)center dot CH3SO3-, GMS) using in situ Raman spectroscopy and synchrotron X-ray diffraction (XRD) techniques up to the pressures of similar to 11 GPa. GMS exhibits the representative supramolecular structure of two-dimensional (2D) hydrogen-bonded bilayered motifs under ambient conditions. On the basis of the experimental results, two phase transitions were identified at 0.6 and 1.5 GPa, respectively. The first phase transition, which shows the reconstructive feature, is ascribed to the rearrangements of hydrogen-bonded networks, resulting in the symmetry transformation from C2/m to Pnma. The second one proves to be associated with local distortions of methyl groups, accompanied by the symmetry transformation from Pnma to Pna2(1). The cooperativity of hydrogen bonding, electrostatic, and van der Waals interactions, as well as mechanisms for the phase transitions is discussed by means of the local nature of the structure.