Health concerns have led to a search for natural plant-based antimicrobials. Ellagic acid has been shown to have antimicrobial activity against foodborne pathogens. The objective of this study was to assess the effect of a high-ellagic acid commercial pomegranate on the heat resistance of Escherichia coli O104:H4 in ground chicken. A full 24 factorial design was used, consisting of temperature treatment with four levels (55.0, 57.5, 60.0, and 62.5 °C) and pomegranate with four levels (0.0, 1.0, 2.0, and 3.0 wt/wt. % containing 70% ellagic acid). Experiments were conducted twice, providing a total of 32 survival curves. A three-parameter Weibull primary model was used to describe survival kinetics. Secondary models were then developed to estimate the shape parameter β (i.e., curvature representing susceptibility of cells to stress), scale parameter γ (i.e., time to reach the first decimal reduction) and the 5.0-log lethality time t5.0 (i.e., time to reach a 5.0-log reduction), all as polynomial functions of temperature and pomegranate powder concentration. The positive effect of pomegranate concentration on both β and γ demonstrated that the phenolic-rich pomegranate powder causes E. coli O104:H4 cells to become more susceptible to heat, increasing the steepness and concavity of the isothermal survival curves. It was estimated that the 5.0-log reduction time would reach a minimum at a pomegranate powder concentration of 1%, producing a 50% decrease in lethality time, in comparison to that without added pomegranate powder. Nonetheless, a mixed-effect omnibus regression further confirmed that the greatest difference in the thermal resistance of E. coli O104:H4 happened between tests with and without pomegranate powder. In fact, adding more than 1.0% pomegranate powder, at a constant temperature, resulted only in a marginal decrease in thermal resistance. Meat processors can use the model to design lethality treatments in order to achieve specific reductions of E. coli O104:H4 in ground chicken.