Fiber based antibacterial materials have gained an enormous attraction for the researchers in these days. In this study, a novel Sericin Encapsulated Silver Nanoclusters (sericin-AgNCs) were synthesized through single pot and green synthesis route. Subsequently these sericin-AgNCs were incorporated into ultrafine electrospun cellulose acetate (CA) fibers for assessing the antibacterial performance. The physicochemical properties of sericin-AgNCs/CA composite fibers were investigated by transmission electron microscopy (TEM), field emission electron microscopy (FE-SEM), Fourier transform infrared spectroscopy (FTIR) and wide X-ray diffraction (XRD). The antibacterial properties of sericin-AgNCs/CA composite fibers against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) were systematically evaluated. The results showed that sericin-AgNCs incorporated in ultrafine CA fibers have played a vital role for antibacterial activity. An amount of 0.17 mg/mL sericin-AgNCs to CA fibers showed more than 90% results and elevated upto >99.9% with 1.7 mg/mL of sericin-AgNCs against E. coli. The study indicated that sericin-AgNCs/CA composite confirms an enhanced antibacterial efficiency, which could be used as a promising antibacterial product.