Various serogroups of Shiga toxin-producing Escherichia coli have been epidemiologically associated with foodborne disease episodes in the United States and around the globe, with E. coli O157: H7 as the dominant serogroup of public health concern. Serogroups other than O157 are currently associated with about 60% of Shiga toxin-producing E. coli related foodborne illness episodes. Current study evaluated sensitivity of the O157 and epidemiologically important non-O157 serogroups of the pathogen to elevated hydrostatic pressure and 1% lactic acid. Pressure intensity of 250 to 650 MPa were applied for 0 to 7 min for inactivation of strain mixtures of wild-type and rifampicin-resistant E. coli O157, as well as O26, O45, O103, O111, O121, and O145 serogroups and ATCC® 43895™ strain in ground meat and 10% meat homogenate. E. coli O157 were reduced (p < 0.05) from 6.86 ± 0.2 to 4.56 ± 0.1 log CFU/g when exposed to pressure of 650 MPa for 7 min. Corresponding reductions (p < 0.05) for non-O157 E. coli were from 6.98 ± 0.3 to 4.72 ± 0.1. The D-values at 650 MPa were 3.71 and 3.47 min for O157 and non-O157 serogroups, respectively. Presence of 1% lactic acid to a great extent augmented (p < 0.05) decontamination efficacy of the treatment in meat homogenate resulting in up to 5.6 and 6.0 log CFU/mL reductions for O157 and non-O157 serogroups, respectively. Among the tested serogroups, the wild-type and rifampicin-resistant phenotypes exhibited (p ≥ 0.05) comparable pressure sensitivity. Thus, these two phenotypes could be used interchangeably in validation studies. Our results also illustrate that, application of elevated hydrostatic pressure could be utilized for assuring safety of ground and non-intact meat products against various serogroups of Shiga toxin-producing E. coli. Addition of 1% lactic acid additionally provided industrially appreciable augmentation in efficacy of the pressure-based treatments.