Methicillin-resistant Staphylococcus aureus (MRSA) is an important human pathogen that can cause serious infectious diseases. An emerging MRSA strain, ST5-SCCmecII spa-type-t2460 (SMRSA), has spread rapidly since its recent emergence in China, but little information is available about this lineage. In this study, 91 MRSA isolates were collected from patients treated in the Zhongnan Hospital, Wuhan University, from 2018 to 2019, and investigated for their molecular characteristics, antibiotic resistance profiles, and clinical characteristics. The predominant lineage, SMRSA, accounted for 37.4% (34/91) of the isolates, followed by ST239-SCCmecIII-t030 (19.8%, 18/91) and ST59-SCCmecIV-t437 (8.8%, 8/91). In contrast to the latter two non-SMRSA (nSMRSA) lineages, which are among the main MRSA found in Chinese settings, SMRSA exhibited small colony variant (SCV) phenotype and had extremely high resistance rates to erythromycin (100.0%), clindamycin (100.0%), levofloxacin (100.0%), tetracycline (97.1%), moxifloxacin (97.1%), and ciprofloxacin (100%), but was more susceptible to rifampicin (resistance rate 3%). The levels of white blood cells (WBC) and procalcitonin (PCT) and the 30-day mortality in patients infected with SMRSA were (12.54 ± 6.61) × 10⁹/L, 0.66 ng/mL, and 52.9%, respectively, which were much higher than those in patients infected with nSMRSA. In addition, patients infected with SMRSA were more frequently admitted to the intensive care unit (ICU) and submitted to invasive procedures than those infected with nSMRSA. In conclusion, SMRSA showed SCV phenotype and exhibited multiple antibiotic-resistance profiles. In this study, SMRSA was associated with serious infections and poor prognosis. Compared with ST239, ST59, or other nSMRSA strains, patients infected with SMRSA strains have higher 30-day mortality, increased levels of inflammatory biomarkers, and more frequent ICU hospitalization and invasive procedures.