Staphylococcus aureus is a major foodborne pathogen and commensal of the skin and mucous membranes of animals and humans. Its virulence relies on the production of a variety of toxins resistant to denaturing conditions. Increasing reports of S. aureus food poisoning and contamination of foods of animal origin elsewhere necessitates the investigation of these foods in Cameroon, to implement safety measures. This cross-sectional study evaluated S. aureus contamination in milk and beef in the Northwest and Southwest Regions of Cameroon, where cow milk is usually not pasteurized before consumption, and beef is the main source of protein. The distribution of antibiotic-resistant isolates and those with enterotoxin-producing potential was also investigated to provide data of public health and food safety benefit. S. aureus was isolated from 39 raw milk and 250 beef samples by standard methods. Confirmation of isolates was by PCR to detect the nuc gene. S. aureus was investigated for classical staphylococcal enterotoxin (SE) genes (sea, seb, sec, sed, and see) by PCR. Their susceptibility to 9 antibiotics was tested by the disk diffusion method. The chi-square test was used to compare the contamination of samples, antibiotic resistance, and the distribution of SE genes. S. aureus was isolated from 11.1% of samples. Contamination was higher in milk (48%) than in beef (5.2%) ( P < 0.001 ). The sea was the most frequently (90%) harboured gene. A large proportion of isolates (88%) harboured more than one virulence gene. Isolates were generally resistant to erythromycin (82%), vancomycin (80%), tetracycline (76%), and oxacillin (74%). Multidrug resistance (MDR) was common (92%). Milk and beef samples in study area were contaminated with MDR enterotoxigenic S. aureus strains and may constitute a potential hazard to consumers. Thus, the need for implementation of proper hygienic measures when handling these products and pasteurization of milk cannot be overemphasized.