Background Staphylococcus aureus can colonize various host species, and human-animal interaction is a significant factor for cross-species transmission. However, data on S. aureus colonization in animals, particularly on ruminants in close contact with humans, is limited. The West African Dwarf (WAD) goat is among the earliest domesticated ruminant associated with rural dwellers and small-holder farmers in sub-Saharan Africa. This study aimed to investigate the population structure, antibiotic resistance, and virulence gene determinants of S. aureus from the WAD goat in Nigeria. Methods Nasal samples were obtained from the WAD goat in five markets in Osun State, South-West Nigeria. S. aureus was characterized by antibiotic susceptibility testing, detection of virulence determinants, spa typing, and multilocus sequence typing (MLST). Representative isolates were selected for whole-genome sequencing, biofilm, and cytotoxicity assay. Results Of the 726 nasal samples obtained from the WAD goat, 90 S. aureus (12.4%) were recovered. Overall, 86 isolates were methicillin-susceptible, and four were mecA-positive (i.e., methicillin-resistant S. aureus [MRSA]). A diverse S. aureus clonal population was observed (20 sequence types [STs] and 37 spa types), while 35% (13/37) and 40% (8/20) were new spa types and STs, respectively. Eleven MLST clonal complexes (CC) were identified (CC1, CC5, CC8, CC15, CC30, CC45, CC97, CC121, CC133, CC152, CC522). The MRSA isolates were designated as t127-ST852-CC1-SCCmec type VII, t4690-ST152-CC152-SCCmec type Vc, and t8821-ST152-CC152-SCCmec type Vc. Phylogenetic analysis revealed that 60% (54/90) of all isolates were associated with ruminant lineages (i.e., CC133, CC522). Panton-Valentine Leukocidin (PVL)-positive S. aureus was identified in CC1, CC30, CC121, and CC152. For the CC522 isolates, we illustrate their pathogenic potential by the detection of the toxic shock syndrome gene and hemolysins, as well as their strong cytotoxicity and ability to form biofilms. Conclusions This is the first detailed investigation on the genomic content of S. aureus from the WAD goat in Nigeria. The S. aureus population of the WAD goat consists mainly of ruminant-associated lineages (e.g., CC133, CC522), interspersed with human-associated clones, including PVL-positive MRSA CC1 and CC152.