Using synchrotron X-ray diffraction and diamond anvil cells we performed in situ high-pressure studies of mullite-type phases of general formula Al4+2xSi2−2xO10−x and differing in the amount of oxygen vacancies: 2:1-mullite (x = 0.4), 3:2-mullite (x = 0.25), and sillimanite (x = 0). The structural stability of 2:1-mullite, 3:2-mullite, and sillimanite was investigated up to 40.8, 27.3, and 44.6 GPa, respectively, in quasi-hydrostatic conditions, at ambient temperature. This is the first report of a static high-pressure investigation of Al2O3–SiO2 mullites. It was found that oxygen vacancies play a significant role in the compression mechanisms of the mullites by decreasing the mechanical stability of the phases with the number of vacancies. Elevated pressure leads to an irreversible amorphization above ~20 GPa for 2:1-mullite and above 22 GPa for 3:2-mullite. In sillimanite, only a partial amorphization is observed above 30 GPa. Based on Rietveld structural refinements of high-pressure X-ray diffraction patterns, the pressure-driven evolution of unit cell parameters is presented. The experimental bulk moduli obtained are as follows: K0 = 162(7) GPa with K0′ = 2.2(6) for 2:1-mullite, K0 = 173(7) GPa with K0′ = 2.3(2) for 3:2-mullite, K0 = 167(7) GPa with K0′ = 2.1(4) for sillimanite.