Here, we demonstrate that PFK amyloid fibrils exhibit remarkable catalytic activity towards βlactam hydrolysis. PFK fibrils, both free-form and displayed on silica beads utilized in conventional water purification settings, were found to catalyze hydrolysis of prominent β-lactam antibiotics, including nitrocefin, penicillin, and amoxicillin. Peptide derivative analysis, complemented by molecular dynamics simulations and cryogenic electron microscopy, point to a unique allosteric catalytic mechanism involving electrostatic interactions of the β-lactam substrates and lysine residues and the formation of coiled fibril structures. This study illuminates amyloid fibrils as a viable platform for antibiotic degradation and removal from water.