High pressure can induce irreversible phase transformations in bulk C60, yet the detailed pathways of phase evolution and strategies to control these processes under extreme conditions remain largely unclear. Here, we investigate the structural transformations of C60 and its supramolecular complex with p-But-calix[8]arene (C60/calix[8]arene) at room temperature under high pressure using a diamond anvil cell (1–20 GPa) and a cubic multi-anvil press (1–15 GPa). Microscopic and spectroscopic characterizations revealed that compression of C60 to 5 GPa yielded a heterogeneous mixture of monomers, dimers, and sp2-rich amorphous phases. Sequential solvent extractions and analyses support a mechanism in which densification and grain refinement promote dimerization along grain boundaries while trapping monomers within crosslinked networks. In contrast, C60 encapsulated within calix[8]arene exhibited fully reversible structural changes under similar conditions, with the layered architecture of the complex providing spatial confinement that prevents pressure-induced polymerization. These findings demonstrate that molecular confinement can suppress fullerene crosslinking under extreme conditions, offering a strategy to tailor the structure and properties of C60-based materials.