The phase transition of the β-HMX crystal has been widely studied under high pressure, but the microscopic transition mechanism is not sufficiently understood. In this article, we perform a series of ab initio molecular dynamics simulations focusing on structure deformation and the corresponding vibration spectra resolution of β-HMX at 0–40 GPa. Several typical pressure-induced phase transition processes are confirmed by analyzing the chemical bond, dihedral angle, charge transfer, and IR and Raman spectra. The corresponding relationship between molecular structure and spectral signal is constructed through the partial spectra calculations of special functional groups within the HMX molecule. The anisotropic effects of different groups on the initial structural phase transition are uncovered. The equatorial C–N and axial N–N bonds have the largest compression ratio as pressure increases, which is the intrinsic factor for the initiation of structure transformation. The C–N molecular ring plays an important role in the entire phase transition process. In addition, the phase transition of β → ζ is also closely related to the deformation of NO₂, while that of ζ → ε is induced by the axial N–NO₂ group. Regarding the higher-pressure phase transition, the synergetic effect of N–NO₂, CH₂ groups, and molecular rings becomes more considerable.