Low-energy proton irradiation effects on the optical properties and the molecular structure of phenyl-C61-butyric acid methyl ester (PCBM) are studied in this work. The PCBM films are irradiated by 100-keV proton beams with fluences of 5 × 1012 p/cm2, 5 × 1013 p/cm2, and 5 × 1014 p/cm2, respectively. The photoluminescence (PL) peaks of the post-irradiated PCBM films show a progressive decrease in the peak intensity as the proton fluences increase, which can be attributed to the deep defect levels induced by proton irradiation. Additionally, a slight blue-shift in the PL spectrum is also observed at a proton fluence of 5 × 1014 p/cm2. The underlying mechanism can be traced back to the lift of the lowest unoccupied molecular orbital (LUMO) level, which is caused by the attachment of methoxy radicals on ortho position of the phenyl ring in the post-irradiated PCBM structure. This work is of significance in understanding the radiation hardness and the damage mechanism of the PCBM film in radiation environments, which is essential before it is put into practical application in space.