'Staphylococcus aureus' is an important human pathogen with an arsenal of virulence factors and a propensity to acquire antibiotic resistance genes. The understanding of the global epidemiology of 'S. aureus' through the use of various typing methods is important in the detection and tracking of novel and epidemic clones in countries and regions. However, detailed information on antibiotic resistance and virulence genes of 'S. aureus', and its population structure is still limited in Africa. In this study, 'S. aureus' isolates collected in South Africa (n = 38) and Nigeria (n = 2) from 2001–2004 were characterized by spa typing and DNA microarray. The combination of these two methods classified the isolates into seven spa types and three clonal complexes (CCs) i.e. t064-CC8 (n = 17), t037-CC8 (n = 8), t1257-CC8 (n = 6), t045-CC5 (n = 5), t951-CC8 (n = 1), t2723-CC88 (n = 1), t6238-CC8 (n = 1), and untypeable-CC8 (n = 1). A high percentage agreement (>95%) and kappa coefficient (>0.60) was largely observed with antibiotic susceptibility testing and DNA microarray, indicating substantial agreement. Some antibiotic and virulence gene markers were associated with specific clones. The detection of the collagen-binding adhesion ('cna') gene was unique for t037-CC8-MRSA while the enterotoxin gene cluster ('egc') and staphylococcal complement inhibitor ('scn') gene were identified with t045-CC5-MRSA. Moreover, the combination of genes encoding enterotoxins ('entA', 'entB', 'entK', 'entQ') was noted with most of the CC8 isolates. The t045-CC5-MRSA clone was positive for the mercury resistance ('mer') operon. DNA microarray provides information on antibiotic resistance and virulence gene determinants and can be a useful tool to identify gene markers for specific 'S. aureus' clones in Africa.