Background: Food-borne diseases related with the consumption of meat and its products had public health importance worldwide and the problem became worst in Ethiopia because of the raw meat eating tradition. Salmonella species and Escherichia coli are important food-borne pathogens associated with meat contamination. Hence this study has been conducted to assess the prevalence and antimicrobial susceptibility of Salmonella species and Extended-spectrum β-lactamase producing Escherichia coli from raw cattle meat at butcher houses in Hawassa city. Method: A cross sectional study was done on prevalence and antimicrobial susceptibility pattern of Salmonella species and Extended-spectrum β-lactamase (ESBL) producing Escherichia coli from raw cattle meat at butcher houses in Hawassa city. Data was collected using a structured questionnaire and raw cattle meat and swab samples taken from surface of meat-cutting equipment. The collected samples were putted into sterile test tube and transported using icebox to Hawassa University College of Medicine and Health Sciences Microbiology Laboratory for identification. Antimicrobial susceptibility tests were determined by using Kirby disc diffusion method. Data was analyzed and entered into SPSS version 23 and descriptive statistics were done and P-value < 0.05 was considered as statistically significant. Result: The overall prevalence of salmonella and ESBL producing E.coliamong 556 samples collected from 278 butcher houses was 36(6.47%)(95% CI: 1.68-1.79) of which 13(2.3%) was ESBL producing E.coli and 23(4.1 %) was salmonella species.Poor hand washing practice (AOR=2.208; 95% CI: 1.249-3.904) and touching birr while selling meat (AOR=0.75; 95% CI: (0.433-1.299) were found to be significantly associated with the prevalence of salmonella species and E.coli on cattle meat. The isolates showed moderate levels of resistance (60–70%) against Amoxicillin/clavu acid and high susceptibility (85-100%) against gentamicin, cotrimoxazole, ceftazidime, and tetracycline. Conclusion: This study revealed moderately high prevalence of salmonella and E.coli due to poor hygiene and sanitation practices in the butcher shops, and existence of ESBL producing E.coli isolates highlight the possible threat to public health, so inspection by the right agencies must be implemented in order to prevent food-borne outbreaks and antimicrobial resistance.