A total of 39 Escherichia coli strains serotype O45, O113, O121, and O157 isolated from cattle in the Mekong Delta were examined the antimicrobial susceptibility to 13 antibiotics by the disc-diffusion method. Those strains were also analyzed for the presence of antibiotic resistance genes by PCR assay, and their genetic relationship by ERIC-PCR assay. The results of antimicrobial susceptibility testing showed that those strains were sensitive to most of the examined antibiotics, but were relatively high resistance to ampicillin (64.10%), and colistin (53.85%). Those E. coli strains could be resistant against one to eight antibiotics with 22 resistance patterns obtained. Moreover, those E. coli strains harbored one to seven antibiotic resistance genes. Gene tetA (51.28%) and blaampC (48.72%) were detected frequently while gene tetB, blaCMY, and cat1 were not found in those E. coli strains. A total of 21 combined patterns of antibiotic resistance genes were recorded, and the most frequent combined pattern was blaampC+tetA (12.82%). ERIC-PCR analysis revealed that each E. coli serotype exhibited various genetic patterns with 40%-100% of similarity. The most elevated number of patterns were in E. coli O157 (nine patterns), followed by E. coli O121 (six patterns). The prevalence of antibiotic resistance genes and diverse genetic characteristics in those E. coli strains originated from cattle constitute potential risks to local health in the Mekong Delta.