Antimicrobial effects of multiple physical, biological and natural interventions on pathogenic Escherichia coli in raw beef were assessed. A cocktail of E. coli strains was inoculated onto gamma-irradiated beef and enumerated immediately after each intervention and during storage at 4 °C for 7 days. Of the physical interventions, silver-containing antimicrobial packaging and ozone gas treatment did not show significant antimicrobial effects, however cold plasma treatment reduced E. coli levels by 0.9 and 1.82 log CFU/cm after 2 and 5 min treatments, respectively. A phage cocktail reduced E. coli counts by 0.63 and 1.16 log CFU/g after 24 h storage at 4 and 12 °C, respectively. Of the natural interventions, vinegar and lactic acid (5%) washes for 5 min caused reductions of ∼1 log CFU/g immediately after treatment, whereas lactoferrin and nisin treatments, separately or in combination, had insignificant antimicrobial effects. Nanoemulsions containing carvacrol or thyme essential oils caused immediate E. coli reductions of 1.41 and 1.36 log CFU/g, respectively, plus a progressive reduction in viable numbers during storage at 4 °C. Our findings suggest that cold plasma, bacteriophages, vinegar, lactic acid, or carvacrol and thyme essential oil nanoemulsions could potentially be of use to the beef industry for controlling pathogenic E. coli contamination.