This study reported an immediate approach for the degradation of three antibiotic (amoxicillin, ofloxacin, and cefradine) residues in medical intravenous infusion bottles (MIIBs) using high energy electron beam (HEEB) irradiation. The effects of irradiation doses, initial concentrations, initial pH, and scavengers of active radicals on the degradation of three antibiotic residues (ARs) were investigated, and the results displayed that 97.02%, 97.61% and 96.87% of amoxicillin, ofloxacin, and cefradine residues could be degraded in situ through HEEB irradiation respectively. Fourier transform infrared spectroscopy (FTIR) and high performance liquid chromatography-mass spectrometry (HPLC-MS) analysis demonstrated that ARs were mainly decomposed into inorganic ions and alkanes. Typically, the detailed degradation mechanism of ARs was also investigated, and the dominant active particle inducing the degradation of antibiotics during the HEEB irradiation process was demonstrated to be hydroxyl radical.