Staphylococcus aureus (S. aureus) is a pathogen capable of causing severe diseases and exhibiting resistance to multiple antibiotics. However, there is a significant lack of comprehensive research on the global prevalence of its antibiotic resistance genes (ARGs). This study provided a comprehensive analysis of ARGs in S. aureus, using 113,842 S. aureus genome sequences from the National Center for Biotechnology Information database. The results revealed that a significant majority (84%) of these genomes harbored at least one ARG, with a total of 389,464 ARG sequences identified across 19 major types and 103 subtypes. These ARGs exhibited varied abundances and diversities, linked primarily to clinical cases worldwide. ARGs for fluoroquinolones, multidrug resistance, bacitracin, tetracyclines, beta-lactams, and aminoglycosides were notably abundant, ranging from 3.16 × 10-5 to 1.49 copies of ARG per million bp. Variations in the abundance and diversity of ARGs were observed between countries, with middle- and low-income countries showing higher gene abundance but lower diversity compared with high-income countries. Temporal analysis over 30 years showed a fluctuating decline in ARG abundance alongside an increase in diversity, suggesting evolving resistance mechanisms. The study also explored the role of mobile genetic elements in ARG dissemination, finding a substantial proportion of ARG subtypes associated with plasmids and insertion sequence elements, indicating their potential for spread across borders. The global distribution of mobile ARGs was further analyzed, revealing the extensive reach of certain ARGs across countries. This research provides valuable insights into the prevalence and dissemination of antibiotic resistance in S. aureus on a global scale, aiding in the development of effective monitoring and control strategies to combat ARGs in S. aureus and other pathogens.