Background: Among Food-borne diseases, S. aureus is a leading cause of gastroenteritis resulting from the consumption of contaminated food. Objectives: The study aimed to isolate and characterize S. aureus from raw milk, yogurt and meat and determine its antibiotic sensitivity pattern. Materials and Methods: A cross-sectional study was conducted from December 2014 to June 2015 in Mekelle. A total of 284 samples were collected purposively. Enumeration of total viable bacteria count (TVBC), bacteriological isolation and identification, antimicrobial susceptibility testing, as well as PCR amplification of fem A and mec A genes were performed. Chi-square (χ 2 ) and one way ANOVA tests were used for analysis. Results: Overall TVBC mean was found to be 1.29x10 8 cfu/ml/g. The highest TVBC (1.38x10 8 cfu/ml) was from the yogurt sample and the lowest (1.26x10 8 cfu/g) was from meat. The overall prevalence of coagulase positive S. aureus (CoPS) was 39.1% (111) and of the smaples, 51(56.04%), 38(26.20%) and 22(45.83%) were isolated from meat, raw milk, and yogurt, respectively. There was a statistically significant difference (p<0.05) among the different sample types and sources in the prevalence of S. aureus . Almost half of the CoPS isolates were sensitive to Tetracycline, Gentamycin, and Kanamycin, but resistant to Amoxicillin (96.9%) and Penicillin G (93.8%). Moreover, 93.75% of the isolates developed multidrug resistance. All isolates carried the fem A gene and among these isolates, 12 (37.5%) carried mec A gene. Conclusion: The present study revealed that foods of bovine origin of the study area are found to be having less bacteriological quality, high prevalence of CoPS and development of drug resistance.