Methicillin-resistant Staphylococcus aureus (MRSA) is a major public health concern due to its resistance and pathogenic potential. This study investigated the prevalence and genetic characterization of MRSA and methicillin-sensitive S. aureus (MSSA) in aquaculture farms in Damietta Governorate, Egypt. Sampling was conducted across three commercial farms cultivating shrimp, marine fish, and freshwater fish. A total of 509 specimens were collected, including 150 shrimp, 75 each of sea bass, sea bream, catfish, and tilapia, 15 farm water samples, and 44 samples from farm workers. S. aureus was isolated using classical techniques and characterized by MALDI-TOF MS, a PbP2a lateral flow assay, and DNA microarrays. Sixty isolates (11.8%) were identified, comprising 46 MRSA and 14 MSSA strains. The carriage rates of S. aureus and MRSA were 6.7% and 4.7% in shrimp, 11.3% and 8.6% in marine fish, 8% and 6.6% in freshwater fish, respectively and were notably higher among farm workers (71.5% and 42.9% in shrimp farms; 50% and 42.9% in marine farms). Four MRSA clonal complexes (CC88, CC361, CC15, CC152) and two MSSA complexes (CC1, CC361) were identified. MRSA CC15 was restricted to shrimp and freshwater fish, while CC152 was found only in workers. Several MRSA clones exhibited multidrug resistance and carried virulence genes encoding leukocidins, hemolysins, proteases, and adhesion & biofilm factors. This is the first report of these clonal complexes in Egyptian aquaculture. The presence of MRSA clones in aquatic ecosystems could represent a significant route for the transmission and spread of multiple pathogenic factors to human populations and emphasize the need to expand monitoring of antimicrobial resistance (AMR) in the study regions.