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Background: Globally, <i>Staphylococcus aureus</i> is an important bacterial pathogen causing a wide range of community and hospital acquired infections. In Ghana, resistance of <i>S. aureus</i> to locally available antibiotics is increasing but the molecular basis of resistance and the population structure of <i>S. aureus</i> in particular in chronic wounds are poorly described. However, this information is essential to understand the underlying mechanisms of resistance and spread of resistant clones. We therefore subjected 28 <i>S. aureus</i> isolates from chronic infected wounds in a rural area of Ghana to whole genome sequencing. Results: Overall, resistance of <i>S. aureus</i> to locally available antibiotics was high and 29% were Methicillin resistant <i>Staphylococcus aureus</i> (MRSA). The most abundant sequence type was ST88 (29%, 8/28) followed by ST152 (18%, 5/28). All ST88 carried the <i>mecA</i> gene, which was associated with this sequence type only. Chloramphenicol resistance gene <i>fexB</i> was exclusively associated with the methicillin-resistant ST88 strains. Panton-Valentine leukocidin (PVL) carriage was associated with ST121 and ST152. Other detected mechanisms of resistance included <i>dfrG</i>, conferring resistance to trimethoprim. Conclusions: This study provides valuable information for understanding the population structure and resistance mechanisms of <i>S. aureus</i> isolated from chronic wound infections in rural Ghana.