The infection in burn wounds covered by biologic dressings leads to wound deepening and chronic wounds. The introduction of silver nanoparticles (AgNPs) into biologic dressings is a beneficial method to prevent wound infection and simultaneously promote wound healing. In this study, an AgNP-loaded silk fibroin (SF)/carboxymethylchitosan (CMC) composite sponge was fabricated. AgNPs with a mean diameter of 4.9 nm was synthesized in SF solution in situ. While CMC was incorporated and chemically crosslinked, SF was insolubilized by ethanol annealing. SEM imaging determined that the AgNP-loaded SF/CMC sponge was more porous than the pure SF sponge. Anti-bacterial results, measured by disk-diffusion and bacterial suspension assay, showed that the AgNP-loaded SF/CMC sponge demonstrated effective anti-bacterial activity against S. aureus and P. aeruginosa, and that its anti-P. aeruginosa activity was higher than that of AQUACEL®; Ag. The introduction of CMC improved the water absorption capacity, retention ability, and water vapor transmission rate of the sponge, which are all important properties of wound dressings.