Beef and beef products have been implicated in several outbreaks involving Shiga-toxinproducing E. coli (STEC). In 2012, six additional STEC besides the commonly implicated E. coli O157: H7 were added to the list of adulterants on beef. An additional complication to the challenge of STEC on beef is the continued isolation of bacteria expressing resistance to at least one antibiotic, some of which have been linked to food borne outbreaks. Several interventions including chemical decontamination are used in the beef industry but, the continued outbreaks and isolation of bacteria on beef allude to the need for more research and improved decontamination technologies. Bacteria exposed to sublethal concentrations of antimicrobials can develop resistance and potential cross-resistance or tolerance to other antimicrobials. The concept of cross-tolerance in bacteria has been evaluated in some studies however none have evaluated antibiotic-resistance (ABR) associated cross tolerance to industrial sanitizers. The goal of the current study was to evaluate cross-tolerance in ABR STEC to sanitizers used in the beef industry. Resistance to ampicillin and streptomycin commonly expressed in ABR STEC isolates were developed in E. coli O157: H7 and the mutant strains were evaluated for phenotypic and genetic changes resulting from the acquisition of ABR. Further, ABR profiles were developed in non O157: H7 STEC and the bacterial strains were evaluated for cross-tolerance to lactic acid (LA) and peroxyacetic acid (PAA). The impact of amino acids rich media on the efficacy of LA and PAA were also evaluated. It was found that ABR in E. coli O157: H7 H1730 increased lag phase duration in the bacteria and improved tolerance to extreme acid stress which was linked to efflux pumps. In the next study, it was found that biofilm formation was also improved in ABR bacteria. Genetic mutations on the efflux pumps contributing towards cross-tolerance were described. The presence of amino acids from beef exudates was observed to significantly increase the bactericidal concentration of PAA for all bacterial strains evaluated. Finally, a novel combination of pelargonic acid and lactic acid was developed and evaluated as an alternative antimicrobial treatment. The results highlight the risks associated with antibiotic associated sanitizer cross-tolerance in STEC and proposes an alternative approach to chemical decontamination.