The escalating burden of infections attributable to methicillin-resistant Staphylococcus aureus (MRSA) in East African countries is calling for interventional strategies to control the spread of this strain. The present study aimed at determining the prevalence, antimicrobial profiles, and staphylococcal cassette chromosome mec (SCCmec) typing of MRSA strains. This was a cross-sectional laboratory-based study involving 226 non-duplicated S. aureus isolates from different clinical samples of patients attending a referral hospital in Kigali. Kirby-Bauer disk diffusion method was used for drug susceptibility testing. Methicillin-resistant S. aureus were confirmed using polymerase chain reaction (PCR) assay for the mecA gene and SCCmec type PCR assay was used for genotyping. Of 138 S. aureus, 39 (31.2%) were found to be MRSA strains. The mean age of the patients was 21.9 years. The incidence of MRSA increases with age and was 27.1% in patient age group younger than 18 years, 33.3% in the age group between 19 and 65 years, and 66.7% in patient age group older than 65 years. There was a significant association between geographic regions and incidence of MRSA (P = 0.02) with the high MRSA isolates from Northern (61.5%) and Western (50%) provinces. Methicillin-resistant S. aureus strains were found to be mostly susceptible to linezolid (93.5%). Among the MRSA strains, SCCmec type I and SCCmec type IV were the most prevalent at 56.4% and 17.9%, respectively. A high prevalence of MRSA was found in Rwanda. Staphylococcal cassette chromosome mec type I (52.2%) was the most predominant. A continuous surveillance of MRSA strains, particularly in the hospital settings, should be an enduring exercise in Rwanda.