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Defense against small molecule toxic gases is an important aspect of protection against chemical and biological threat as well as chemical releases from industrial accidents. Current protective respirators/garments cannot effectively block small molecule toxic gases and vapors and retain moisture transmission capability without a heavy burden. Here, we developed a nanopacked bed of nanoparticles of UiO-66-NH₂ metal organic framework (MOF) by synthesizing them in the pores of microporous expanded polytetrafluoroethylene (ePTFE) membranes. The submicron scale size of membrane pores ensures a large surface area of MOF nanoparticles which can capture/adsorb and react with toxic gas molecules efficiently. It was demonstrated that the microporous ePTFE membrane with UiO-66-NH₂ MOF grown inside and around the membrane can defend against ammonia for a significant length of time while allowing passage of moisture and nitrogen. It was also demonstrated that the MOF-loaded ePTFE membrane could provide significant protection from Cl₂ intrusion as well as intrusion from 2-chloroethyl ethyl sulfide (CEES) (a simulant for sulfur mustard). Such MOF-filled membranes exhausted by NH₃ breakthrough experiments were regenerated conveniently by heating at 60 °C for one week under vacuum for further/repeated use; a single regenerated membrane could block NH₃ for 200–300 min. The moisture permeability of such a membrane/nanopacked bed was considerably above the breathability threshold value of 2000 g/m² -day. The results suggest that microporous membranes filled with reactive MOF nanoparticles could be designed as protective barriers against toxic gases/vapors, e.g., NH₃ and Cl₂ and yet be substantially permeable to H₂O and air.