The identification and characterization of low-frequency vibrational motions of metal-organic frameworks (MOFs) allows for a better understanding of their mechanical and structural response upon perturbation by external stimuli such as temperature, pressure, and adsorption. Here, we describe the combination of an experimental temperature- and pressure-dependent terahertz spectroscopy system with quantum mechanical simulations to measure and assign specific low-frequency vibrational modes that directly drive the mechanochemical properties of this important class of porous materials. More specifically, those intense spectral features in the terahertz region of the vibrational spectrum of ZIF-8 are identified, which are directly connected to its mechanochemical response. In particular, the mechanical compressibility of pristine ZIF-8 is found to follow a peculiar non-linear trend upon pressure: its bulk modulus initially increases up to 0.1 GPa and decreases at higher pressures, which is simultaneously reflected in the terahertz vibrational spectra. This work highlights the interplay between structural, vibrational, and mechanochemical phenomena, all of which are key to the effective exploitation of MOFs. The importance of terahertz vibrational motions on the function of MOFs is demonstrated, and a method presented for their measurement and interpretation, which can be applied widely to any supramolecular material.