The most significant community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) in Korea is sequence type (ST) 72 with staphylococcal cassette chromosome mec (SCCmec) type IV (ST72-MRSA-IV). Although the impact of CA-MRSA on the clinical outcomes versus healthcare-associated (HA)-MRSA remains unclear, it has recently been revealed that ST5 HA-MRSA-II is associated with higher mortality compared with ST72 CA-MRSA-IV, suggesting higher virulence in ST5 HA-MRSA-II strains. In this investigation, human-/animal-originated ST72-MRSA-IV strains were examined for virulence phenotypes and compared with those of ST5-MRSA-II strains, the established HA-MRSA in Korea. Overall, ST5 HA-MRSA-II strains demonstrated higher levels of resistance to host defense-cationic antimicrobial peptides of human (LL-37), bovine (BMAP-28), and bacterial (polymyxin B) origins versus ST72-MRSA-IV strains via enhanced surface positive charge. Hemolysis profiles, gelatinase activity, and staphylococcal superantigen gene profiles were not different between ST72 CA-MRSA and ST5 HA-MRSA strains. However, ST5 HA-MRSA strains were able to downregulate initial cytokine response in murine macrophages.