Foodborne infections are widespread and growing public health problems in the world. Shiga toxin-producing Escherichia coli O157 : H7 is one of the most significant foodborne pathogens. This study was conducted to assess the occurrence and antibiogram of E. coli O157 : H7 from raw beef as well as hygienic and sanitary practices of meat handling in abattoir and retailer shops. Systematic random sampling technique and census methods were used to collect samples from abattoir and retailer shops, respectively. All tryptone soya broth preenriched carcass samples were subcultured onto MacConkey agar. Then, the bacterium confirmed as Escherichia coli using biochemical tests was streaked onto Sorbitol-MacConkey agar and incubated at 37°C for 24 hrs. Escherichia coli O157 : H7 was confirmed by latex agglutination kit. In vitro antimicrobial susceptibility test of Escherichia coli O157 : H7 isolates was done against 13 antimicrobials. Hygiene and sanitation data were collected using a pretested structured questionnaire and observational checklist. Pearson Chi-square and Fisher’s exact two-tailed tests were performed and differences were considered significant at P ≤ 0.05. Out of 197 meat samples, 23.4% (95% confidence interval (CI): 17.6–29.9%) and 9.1% (95% CI: 5.5–14.1%) were contaminated with Escherichia coli and Escherichia coli O157 : H7, respectively. There was a significant variation in the occurrence of Escherichia coli O157 : H7 between retailer shops (19.1%) and abattoir (7.2%) (P = 0.03). The study revealed that the municipal abattoir and retailer shops in Ambo town did not adhere to the required sanitation and hygienic standards. All Escherichia coli O157 : H7 isolates were susceptible to norfloxacin, sulfamethoxazole-trimethoprim, chloramphenicol, and ceftazidime. However, all isolates were resistant to amoxicillin. Multidrug resistance was widespread and was found in 66.3% of Escherichia coli O157 : H7 isolates. The occurrence of Escherichia coli O157 : H7 was high. Therefore, fulfilling national and international meat safety requirements, training and monitoring of meat handlers, and rational use of antimicrobials are recommended