White brined cheese may serve as an ideal medium for the growth of foodborne pathogens including E. coli O157:H7. The objectives of this study were i) to evaluate the inhibitory effects of zinc oxide (ZnO) nanoparticles against E. coli O157:H7 at 10 or 37 °C using broth dilution; ii) to address the post-process contamination of white brined cheese with E. coli O157:H7 by using chitosan coating with or without ZnO nanoparticles during storage for 28 d at 4 and 10 °C; and iii) to study the physicochemical characteristics of chitosan coating containing ZnO nanoparticles. ZnO nanoparticles at ≥0.0125% inhibited the growth of three E. coli O157:H7 strains at both 37 and 10 °C. The chitosan coating with or without ZnO nanoparticles significantly reduced the initial numbers of E. coli O157:H7 in white brined cheese by 2.5 and 2.8 log CFU/g, respectively, when stored at 4 °C or by 1.9 and 2.1 log CFU/g, respectively, when stored at 10 °C. The chitosan-ZnO nanoparticle coating was not significantly different (p > 0.05) but was slightly better than chitosan alone as an active, smart packaging material in food applications.