<p>Carbapenem-resistant <i>Klebsiella pneumoniae</i> (CRKP), particularly strains producing <i>Klebsiella pneumoniae</i> carbapenemase (KPC), pose a severe global health challenge due to limited therapeutic options and high mortality. While ST11 is the predominant KPC-producing lineage in China, the clinical and epidemiological significance of ST656 remains largely unexplored. We conducted a genomic and epidemiological investigation of twenty-five KPC-2-producing <i>K. pneumoniae</i> ST656 isolates collected from patients with severe pulmonary comorbidities in a tertiary hospital in Eastern China between July 2020 and October 2021. Antimicrobial susceptibility testing, whole-genome sequencing (WGS), phylogenetic analysis, plasmid profiling and conjugation assays were performed to determine resistance mechanisms, clonal relationships and plasmid transferability. Clinical information showed all 25 isolates originated from distinct patients in a tertiary hospital in Eastern China, predominantly older male post-lung transplantation cases with severe pulmonary disease, from intensive care units and thoracic surgery wards. All isolates displayed highly similar multidrug-resistant profiles, being resistant to most β-lactams, levofloxacin and trimethoprim-sulfamethoxazole, with limited susceptibility to amikacin and tigecycline. Genomic characterization of representative strain CRE132 showed that <i>bla</i>_KPC−2 was located on a conjugative IncFII plasmid, and that this plasmid could transfer carbapenem resistance to <i>Escherichia coli</i> in conjugation assays. ST656 isolates in our study exhibited modest increase in virulence-associated traits, growth rates and certain adaptability compared with ST11 isolates. This study represents the first genomic and epidemiological investigation demonstrating nosocomial clonal dissemination of KPC-2–producing <i>K. pneumoniae</i> ST656 in China. These findings highlight the importance of continued genomic surveillance and improved understanding of this emerging lineage.</p>