Background: Staphylococcus aureus (S. aureus) is a leading cause of skin and soft tissue infections. The prevalence of methicillin-resistant (MRSA) and multidrug-resistant (MDR) strains has been increasing globally in recent years. In Mongolia, data on MRSA prevalence and antimicrobial susceptibility in purulent skin infections remain limited. Aim: To assess the prevalence of MRSA and MDR S. aureus and their antimicrobial susceptibility patterns in purulent skin infections. Materials and Methods: This laboratory-based retrospective study analyzed 22,753 samples collected between 2015−2025 at the National Dermatology Center of Mongolia, in which S. aureus was identified. MDR was defined according to the Magiorakos criteria as resistance to three or more antibiotic classes. Prevalence was expressed with 95% confidence intervals (CI). Group differences were assessed using the chi-square (χ²) test; and age- and sex-related risks were estimated using odds ratios (OR) with 95% CI. A p-value <0.05 was considered statistically significant. Results: MRSA was detected in 18.8% (n=4,278) and MDR in 40.7% (n=9,258) of cases. The prevalence of MRSA increased significantly from 0–1.6% during 2015–2019 to 15–34.2% during 2020–2025 (p<0.001). MDR prevalence peaked at 53.9% (n=1,682) in 2022. No statistically significant sex differences were observed for MRSA (female: 2,331; male: 1,947) or MDR (female: 4,958; male: 4,300) (p>0.05). MRSA prevalence was highest in children under 1 year (47.4%) and lowest in those aged 15–24 years (14.8%), while MDR prevalence increased significantly with age and was highest among individuals aged ≥81 years (p<0.001). The presence of MRSA was associated with a 16.76-fold higher likelihood of MDR S. aureus (p<0.001). Antibiotic resistance was highest for penicillin-class antibiotics (ampicillin 91.5%, amoxicillin 75.4%), whereas susceptibility remained high for vancomycin (4.4% resistance), nitrofurantoin (4.6%), and amikacin (10.1%). Conclusion Over the past decade, the prevalence of MRSA and MDR S. aureus in purulent skin infections has increased markedly. Although resistance to penicillin-class antibiotics remains high, susceptibility to vancomycin and nitrofurantoin is largely preserved. The higher prevalence observed in younger and older age groups highlights the need to strengthen infection control measures and promote the rational use of antibiotics.