Methicillin-resistant Staphylococcus aureus (MRSA) infections of soft tissues and deep and superficial wounds affect morbidity, mortality, and healthcare resources in Saudi Arabia. The growing frequency of these infections underscore the need for effective antimicrobial stewardship projects and robust infection control. This study included patients from various age groups and was conducted in a tertiary care facility in Riyadh. Clinical specimens from different body parts were cultured, as part of the study protocol. Samples showing significant Staphylococcus aureus (S. aureus) growth were identified phenotypically and tested for microbial susceptibility. Antibiotics were evaluated and analyzed according to Clinical and Laboratory Standards Institute (CLSI) guidelines. MRSA isolates were screened using cefoxitin discs. Data was gathered and analyzed over one year, from January to December 2023. This study included 11,837 culture specimens, of which 3,795 yielded positive cultures. S. aureus was isolated in 333 cases, accounting for 2.8% of all specimens, and 8.8% of positive cultures. Most patients were male, comprising 121 study participants (36%). The highest MRSA prevalence was observed between 12 and 40 years. The prevalence of MRSA in the local healthcare environment was 3.3%. Hospitalized patients showed a slightly higher incidence of MRSA infection. MRSA prevalence was significantly associated with the specimen type (p < 0.05). Vancomycin and linezolid were 100% effective against all S. aureus strains, followed by tetracycline and gentamicin. The D-test was used to assess 307 S. aureus strains to assess inducible clindamycin resistance, 28 tested positive. The high MRSA infection load and new MRSA strains highlight the need for ongoing surveillance, stringent infection control, and targeted antibiotic stewardship programs. Our findings could be used to guide antibiotic treatment and combat antibiotic resistance in local hospitals.