This study investigates the global distribution and spatiotemporal characteristics of carbapenem-resistant *Escherichia coli* (CREC) across 75 countries, focusing on 7918 isolates from 497 sequence types (ST). The research reveals a transition from highly virulent ST131 and ST38 to more antibiotic-resistant ST410 and ST167 over the past decade. The spread of CREC is associated with the increasing prevalence of resistance genes such as *bla*NDM-5, *bla*OEC-2, and *bla*OXA-48, and plasmids like IncFI, IncFII, and IncI. Intercontinental transfers of major CREC strains are observed, with specific hubs identified for ST131 in the UK, Italy, the US, and China; ST167 in India, France, Egypt, and the US; and ST410 in Thailand, Israel, the UK, France, and the US. The study highlights the importance of understanding CREC's genetic diversity, antibiotic resistance profiles, and virulence characteristics to manage and prevent infections in healthcare settings and among diverse hosts.This study investigates the global distribution and spatiotemporal characteristics of carbapenem-resistant *Escherichia coli* (CREC) across 75 countries, focusing on 7918 isolates from 497 sequence types (ST). The research reveals a transition from highly virulent ST131 and ST38 to more antibiotic-resistant ST410 and ST167 over the past decade. The spread of CREC is associated with the increasing prevalence of resistance genes such as *bla*NDM-5, *bla*OEC-2, and *bla*OXA-48, and plasmids like IncFI, IncFII, and IncI. Intercontinental transfers of major CREC strains are observed, with specific hubs identified for ST131 in the UK, Italy, the US, and China; ST167 in India, France, Egypt, and the US; and ST410 in Thailand, Israel, the UK, France, and the US. The study highlights the importance of understanding CREC's genetic diversity, antibiotic resistance profiles, and virulence characteristics to manage and prevent infections in healthcare settings and among diverse hosts.