By combining solvent evaporation with wet phase inversion technique, an asymmetric polyurethane membrane (ASPU) was constructed from a sulfanilamide-conjugated PU, as a potential candidate for wound dressing application. As a result of the combined membrane-formation method, the ASPU membrane was constituted by an integral and dense skin layer supported by a porous sublayer. The skin layer was found impermeable to pathogenic organisms, while the sublayer was intended for draining excessive exudates. Compared with typical PU membrane dressings commercially available, the ASPU membrane exhibited a reasonable moisture vapor transmission rate, as well as significantly improved gas circulation and exudate absorption capabilities, which synergistically optimized the wound microenvironment for proper healing. Furthermore, the sulfanilamide-conjugated PU constituting ASPU membrane was designed as susceptible to urease, a representative hydrolase derived from inflammation-causing pathogens. In the presence of urease, urea linkages adjacent to sulfanilamide monomeric units were found catalytically cleaved, enabling release of free antibiotic sulfanilamide that held pharmacological activity from ASPU membrane. When incubated without urease, those cleavage sites exhibited substantially high resistance against hydrolysis so that no sulfanilamide release was detected throughout the incubation period. In this inflammation-responsive manner, the anti-inflammatory efficiency of antibiotics was significantly enhanced, while undesirable side effects associated with antibiotic abuse was minimized. Cell culture assay further revealed that the ASPU membrane displayed no cytotoxicity toward normal human dermis fibroblasts, suggesting a biocompatible potential. Based on these results, the multifunctional ASPU membrane designed in this study might be clinically suitable as an ideal biomedical dressing for wound care.