Carbapenem-resistant *Escherichia coli* (CREC) ST410 has emerged as a significant global health concern. This study reports a shift in CREC prevalence in Chinese hospitals from 2017 to 2021, with ST410 becoming the most commonly isolated sequence type. Genomic analysis identifies a hypervirulent CREC ST410 clone, designated B5/H24RxC, which caused two separate outbreaks in a children's hospital. B5/H24RxC likely emerged from the previously characterized B4/H24RxC clone, which was first identified in 2006. B5/H24RxC lacks the *bla*OXA-181-bearing X3 plasmid but carries a F-type plasmid containing *bla*NDM-5. Most B5/H24RxC isolates also carry a high pathogenicity island and a novel O-antigen gene cluster. Comparative genomic analyses reveal that B5/H24RxC has a higher growth rate in vitro and is more virulent in vivo compared to B4/H24RxC. The identification of this newly emerged but already globally disseminated hypervirulent CREC clone highlights the ongoing evolution of ST410 towards increased resistance and virulence.Carbapenem-resistant *Escherichia coli* (CREC) ST410 has emerged as a significant global health concern. This study reports a shift in CREC prevalence in Chinese hospitals from 2017 to 2021, with ST410 becoming the most commonly isolated sequence type. Genomic analysis identifies a hypervirulent CREC ST410 clone, designated B5/H24RxC, which caused two separate outbreaks in a children's hospital. B5/H24RxC likely emerged from the previously characterized B4/H24RxC clone, which was first identified in 2006. B5/H24RxC lacks the *bla*OXA-181-bearing X3 plasmid but carries a F-type plasmid containing *bla*NDM-5. Most B5/H24RxC isolates also carry a high pathogenicity island and a novel O-antigen gene cluster. Comparative genomic analyses reveal that B5/H24RxC has a higher growth rate in vitro and is more virulent in vivo compared to B4/H24RxC. The identification of this newly emerged but already globally disseminated hypervirulent CREC clone highlights the ongoing evolution of ST410 towards increased resistance and virulence.