Antimicrobial resistance (AMR) poses a critical challenge to global health, as pathogenic microorganisms increasingly evade traditional therapies. Addressing this, we report an antimicrobial nanocomposite, prepared by atomic layer deposition (ALD) of a high area, conformal ZnO ultrathin film over mesoporous silica (SBA-15). Photophysical characterisation of the ZnO/SBA-15 composite revealed well-defined mesopores, a high surface area of 790 m2 g−1, and an optical band gap of 3.25 eV, suitable for light-responsive applications. Antimicrobial efficacy of ZnO/SBA-15 was tested against Escherichia coli 0157, a common Gram-negative bacterium found in water systems and resistant to standard antibiotics. ZnO/SBA-15 showed a 0.51 log reduction in bacterial colony counts in 1 h at a ZnO concentration of 2 mg/mL under UV light, significantly outperforming ZnO nanoparticles and SBA-15 alone by 47 and 33 %, respectively. This enhanced bacteriostatic activity is attributed to efficient reactive oxygen species generation facilitated by the ZnO ultrathin film, demonstrating the utility of ALD to coat complex 3D architectures to combat AMR in water treatment or biomedical applications.