An experimental study on ordered pyrochlore structured Gd1.5Ce0.5Ti2O7 (Fd-3m) was carried out up to 45 GPa by synchrotron radiation X-ray diffraction and Raman spectroscopy. Experimental results show that Gd1.5Ce0.5Ti2O7 transfers to a disordered cotunnite-like phase (Pnma Z=4) at ~42 GPa. Compared with the end member Gd2Ti2O7, the substitution of Ce3+ for Gd3+ increases the transition pressure and the high-pressure stability of the pyrochlore phase. This pressure-induced structure transition is mainly controlled by cationic order-disorder modification, and the cationic radius ratio rA/rB may also be effective for predicting the pyrochlore oxides’ high-pressure stability. In addition, two isostructural transitions of Gd1.5Ce0.5Ti2O7 are observed at 6.5 GPa and 13 GPa, and their unit-cell volumes as a function of pressure demonstrate that the compression behavior is rather complex.