Synchrotron X-ray powder diffraction and infrared (IR) spectroscopy studies on natural brucite were conducted up to 31 GPa using diamond-anvil cell (DAC) techniques at beamlines X17C and U2A of National Synchrotron Light Source (NSLS). The lattice parameters and unit-cell volumes were refined in P3̄m1 space group throughout the experimental pressure range. The anisotropy of lattice compression decreases with pressure due to a more compressible c axis and the compression becomes nearly isotropic in the pressure range of 10–25 GPa. The unit-cell volumes are fitted to the third-order Birch-Murnaghan equation of state, yielding K0 = 39.4(1.3) GPa, K0′ = 8.4(0.4) for the bulk modulus and its pressure-derivative, respectively. No phase transition or amorphization was resolved from the X-ray diffraction data up to 29 GPa, however, starting from ~4 GPa, a new infrared vibration band (~3638 cm−1) 60 cm−1 below the OH stretching A2u band of brucite was found to coexist with the A2u band and its intensity continuously increases with pressure. The new OH stretching band has a more pronounced redshift as a function of pressure (−4.7 cm−1/GPa) than the A2u band (−0.7 cm−1/GPa). Comparison with first-principles calculations suggests that a structural change involving the disordered H sublattice is capable of reconciling the observations from X-ray diffraction and infrared spectroscopy studies.