Antimicrobial resistance (AMR) is a critical global health crisis that is projected to cause up to 10 million deaths annually by 2050. Staphylococcus aureus presents significant challenges, particularly in Africa. This study examined the diversity of antimicrobial resistance genes (ARGs) in S. aureus isolates from food sources across Africa. ARGs were identified via the ResFinder database and ABRIcate (version 1.0.1) with a DNA identity and coverage cutoff of 80%. Data from the European Nucleotide Archive were analyzed, and visualizations such as bar charts, heatmaps, and network graphs were generated via Matplotlib and NetworkX in Python. The analysis revealed significant multidrug resistance in Staphylococcus aureus across four African countries. In Egypt, the blaZ gene is resistant to a wide range of antibiotics, with the mecA gene exhibiting extensive multidrug resistance. Ghana displayed high resistance levels across multiple antibiotic classes, with notable genes being blaZ and mecA. Nigeria had significant resistance linked to blaZ and dfrG genes, indicating resistance to multiple antibiotics, including trimethoprim. Rwanda showed resistance patterns associated primarily with the blaZ and cat(C221) genes, indicating chloramphenicol resistance and moderate resistance to other antibiotics. This study highlights the resistance profiles of S. aureus across these four African countries, emphasizing the urgent need for coordinated global efforts to combat antibiotic resistance. The findings underscore the importance of improved antibiotic stewardship in African food production and handling alongside enhanced surveillance programs to monitor trends and inform policy decisions.