Objectives . Carbapenem-resistant Klebsiella pneumoniae (CRKP) strains harbouring bla _KPC and bla _NDM are prevalent in China, while bla _OXA-48 -positive CRKP remains uncommon. This study reports one of the first outbreaks of a nosocomial infection caused by ST101 bla _OXA-48 -positive CRKP in China. Methods . We conducted a retrospective molecular epidemiological study of 269 CRKP isolates collected at a tertiary hospital in China, between 2012 and 2022. Antimicrobial susceptibility testing, whole-genome sequencing, phylogenetic analyses and plasmid characterization were performed to investigate the clinical and molecular features of bla _OXA-48 -CRKP. Conjugation assays were used to assess plasmid transferability. Results . Among the 269 CRKP isolates, we identified 61 bla _OXA-48 -positive strains from 38 patients. Most cases were linked to the intensive care unit (ICU), with patient transfers facilitating spread to non-ICU wards and branch hospitals. The outbreak was associated with a high mortality rate (63.2%), including 42.1% within 30 days. Genomic analysis revealed that 59 isolates belonged to ST101 and carried multiple resistance determinants. All bla _OXA-48 genes were located on IncL plasmids, which evolved into three structural variants during the outbreak. Notably, the late-emerging Type III plasmid had lost conjugative transferability. Core-genome SNP analysis demonstrated clonal expansion within the hospital, while phylogenetic comparisons indicated the likely introduction of ST101 strains from Europe. Global phylogenomic analysis revealed complex intercontinental transmission pathways, underscoring the lineage’s high potential for global dissemination. Conclusions . We documented the first hospital outbreak in China caused by ST101 bla _OXA-48 -positive CRKP. This study improves our understanding of plasmid evolution during nosocomial outbreaks and provides valuable insights to guide infection control strategies of plasmid-mediated resistance.