Elastic fibers have been widely applied for the fabrication of biomedical textiles, artificial extracellular matrix, and functional garments, as where antibacterial property is one of the indispensable features. Herein, we developed a fresh type of non‐leaching antibacterial fiber that could effectively inactivate bacteria with durable performance to circumvent above concerns. In detail, we firstly synthesized a precursor polymer (PS‐GMA) based on styrene and glycidyl methacrylate (GMA) through free radical polymerization, then blended PS‐GMA with thermoplastic polyurethane (TPU) and processed the blend into fiber through wet spinning technology. Finally, the obtained fiber was covalently modified by polyhexamethylene biguanide hydrochloride (PHMB). The experimental results showed that the resultant fiber (named as PGPs) exhibited a strong bactericidal ability to both Staphylococcus aureus and Escherichia coli, as well as maintained excellent antibacterial properties even after ultraviolet irradiation for 7 days or 50 washing cycles. Furthermore, we explored the sterilization mechanism with respect to the bacterial morphologies and the activity of the respiratory chain dehydrogenase. In addition, the biocidal efficacy of the prepared fiber could remain approximately 100% after eight consecutive antibacterial cycles. Collectively, this work exhibited an attempt in exploitation of the intrinsically antibacterial fiber with long‐run function duration by an economical tactic.