Lignin-capped silver nanoparticles were incorporated in situ into polyurethane foams during their polymerization to obtain multifunctional materials suitable for chronic wound dressing. Lignin with increased phenolic content, achieved through the enzymatic grafting of natural phenolic compounds, played the dual role of a silver reducing agent in the synthesis of the lignin-capped silver nanoparticles and as a nanoformulated polyol additive in the polyurethane composition able to react with isocyanate. The nanoparticles-embedded polyurethane foams showed over 4 and 5 logs bacterial growth reduction against the Gram-positive S. aureus and the Gram-negative P. aeruginosa, respectively, attributed to both the direct contact- and release-killing mechanisms. The swelling properties of the foams, related to their capacity to remove the excess of wound exudates containing deleterious oxidative species and enzymes, varied from 585 to 1145% as a function of the content of nanoparticles. Overall, the physicomechanical and antibacterial properties of the foams, together with their biocompatibility and sustained release of silver, make these multifunctional materials suitable candidates for chronic wound dressings.