The current study investigated synergism of elevated hydrostatic pressure, habituation, mild heat, and antimicrobials for inactivation of O157 and non-O157 serogroups of Shiga toxin-producing Escherichia coli. Various times at a pressure intensity level of 450 MPa were investigated at 4 and 45 °C with and without carvacrol, and caprylic acid before and after three-day aerobic habituation in blueberry juice. Experiments were conducted in three biologically independent repetitions each consist of two replications and were statistically analyzed as a randomized complete block design study using ANOVA followed by Tukey- and Dunnett’s-adjusted mean separations. Under the condition of this experiment, habituation of the microbial pathogen played an influential (p < 0.05) role on inactivation rate of the pathogen. As an example, O157 and non-O157 serogroups were reduced (p < 0.05) by 1.4 and 1.6 Log CFU/mL after a 450 MPa treatment at 4 °C for seven min, respectively, before habituation. The corresponding log reductions (p < 0.05) after three-day aerobic habituation were: 2.6, and 3.3, respectively at 4 °C. Carvacrol and caprylic acid addition both augmented the pressure-based decontamination efficacy. As an example, Escherichia coli O157 were reduced (p < 0.05) by 2.6 and 4.2 log CFU/mL after a seven-min treatment at 450 MPa without, and with presence of 0.5% carvacrol, respectively, at 4 °C.