Infectious pathogens, such as SARS-CoV-2, can remain viable on common fabric surfaces for days, posing a significant risk of fomite transmission. Antimicrobial coatings are a widely employed approach for pathogen eradication upon direct contact. However, fabricating such coatings on fabric substrates mostly necessitates toxic organic solvents and complex equipment/ procedures. Most coatings also require a long contact time for complete disinfection, which may compromise their usefulness in mitigating the spread of highly infectious pathogens. Herein, we report a sustainable and scalable water-mediated method to prepare a copper iodide (CuI) coating on flexible cotton fabrics, attaining highly potent antimicrobial efficacy and rapid germicidal kinetics. Only water is required as the processing solvent for the in situ formation of CuI nanoparticles on the substrate, and the unconsumed reagents can be fully recycled, making the reported method a green, economical, and zero-waste technology promising for industrial scale-up. Within just 2 min of contact, the coated cotton fabric containing 5.1 wt % CuI nanoparticles exhibits near-complete inactivation of murine hepatitis coronavirus (>99.9%) and Salmonella bacteriophage P22 (>99.9999%) as models for the enveloped and nonenveloped viral species, respectively. It is also able to eliminate a variety of bacteria and fungi with 3.5−7.4 log reductions in 2−5 min. Furthermore, in view of the robust durability and skin compatibility of the coating, this simple yet powerful approach holds great promise for practical applications, especially in future infectious disease outbreaks.