Background: Staphylococcus aureus is a Gram-positive bacteria pathogen responsible for both community acquired and healthcare associated infections. Methicillin-resistant S. aureus (MRSA) remains a significant global health concern due to its high morbidity and mortality. This study investigated the phenotypic and molecular detection of mecA and mecC genes in S. aureus isolates from patients admitted to the emergency unit of a tertiary healthcare facility in Lagos, Nigeria. Methods: This is a cross-sectional study conducted in an emergency unit of Lagos University Teaching Hospital Idi-Araba Lagos. Consenting adult patients admitted in emergency unit were enrolled into the study. It was conducted between Ist June, 2019 to 30th May, 2020. Result: A total of 300 patients clinically diagnosed with infections were recruited for the study. Staphylococcus aureus was identified as the causative agent in 43 of these cases. Female patients constituted 51.2% of those infected, while males accounted for 48.8%. The prevalence of methicillin-resistant Staphylococcus aureus (MRSA) among the isolates was 41.8%. All MRSA isolates carried the mecA gene, and one isolate was found to possess both mecA and mecC genes. Conclusion: The observed high prevalence of MRSA and the presence of both mecA and mecC genes highlight the epidemiological significance of this study. Continuous antibiotic resistance monitoring and routine screening for methicillin-resistant Staphylococcus aureus are therefore strongly recommended.