Zinc oxide (ZnO) nanoparticles were synthesized and deposited on the surface of cotton fabrics using ultrasound irradiation. Optimization of the process resulted in a homogeneous distribution of ZnO nanocrystals, 30 nm in size, on the fabric surface. The mechanism of the ultrasound-assisted coating was proposed. The antibacterial activities of the ZnO-fabric composite were tested against Escherichia coli (Gram negative) and Staphylococcus aureus (Gram positive) cultures. A significant bactericidal effect, even in a 0.75% coated fabric (wt %), was demonstrated.