This study investigates the global distribution and spatiotemporal characteristics of carbapenem-resistant Escherichia coli (CREC) across 7918 isolates from 75 countries and 497 sequence types (STs). The research reveals a shift in dominant STs from highly virulent ST131 and ST38 to more antibiotic-resistant ST410 and ST167 over the past decade. The spread of CREC is linked to the transmission of resistance genes such as blaNDM-5, blaKPC-2, and blaOXA-48, as well as plasmids like IncFI, IncFII, and IncL. Major CREC strains have been identified in various regions, including 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 transmission patterns to manage infections and prevent their spread in healthcare settings and among diverse hosts. Antimicrobial resistance is a major global public health challenge, with over 700,000 deaths annually from infections caused by resistant microbes. CREC, resistant to carbapenems, is a critical priority organism for new antibiotics. It causes severe infections and is a major food safety concern. CREC strains often carry multiple resistance genes, complicating treatment and increasing the risk of transmission. The study shows that CREC has evolved into a complex resistant strain rather than a single, stable resistant strain. CREC is found in multiple regions globally, with notable regional variations in prevalence and spread. The study provides insights into the distribution and transmission of CREC across different countries and continents, emphasizing the need for global surveillance and control measures. The study analyzed the prevalence of antibiotic resistance genes (ARGs) and virulence factors in CREC strains, revealing a significant increase in the prevalence of ARGs on plasmids from 2018 to 2023. The prevalence of certain ARGs, such as sulfonamide-resistant genes and ESBL resistance genes, has increased, while the prevalence of plasmid-borne CRGs has decreased. The study also identified key transmission hubs for various STs, highlighting the importance of monitoring and controlling CREC transmission. The findings underscore the need for comprehensive strategies to address the global challenge of antimicrobial resistance, including the implementation of policies to restrict the use of carbapenem antibiotics and the integration of the "One Health" framework for prevention and control.This study investigates the global distribution and spatiotemporal characteristics of carbapenem-resistant Escherichia coli (CREC) across 7918 isolates from 75 countries and 497 sequence types (STs). The research reveals a shift in dominant STs from highly virulent ST131 and ST38 to more antibiotic-resistant ST410 and ST167 over the past decade. The spread of CREC is linked to the transmission of resistance genes such as blaNDM-5, blaKPC-2, and blaOXA-48, as well as plasmids like IncFI, IncFII, and IncL. Major CREC strains have been identified in various regions, including 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 transmission patterns to manage infections and prevent their spread in healthcare settings and among diverse hosts. Antimicrobial resistance is a major global public health challenge, with over 700,000 deaths annually from infections caused by resistant microbes. CREC, resistant to carbapenems, is a critical priority organism for new antibiotics. It causes severe infections and is a major food safety concern. CREC strains often carry multiple resistance genes, complicating treatment and increasing the risk of transmission. The study shows that CREC has evolved into a complex resistant strain rather than a single, stable resistant strain. CREC is found in multiple regions globally, with notable regional variations in prevalence and spread. The study provides insights into the distribution and transmission of CREC across different countries and continents, emphasizing the need for global surveillance and control measures. The study analyzed the prevalence of antibiotic resistance genes (ARGs) and virulence factors in CREC strains, revealing a significant increase in the prevalence of ARGs on plasmids from 2018 to 2023. The prevalence of certain ARGs, such as sulfonamide-resistant genes and ESBL resistance genes, has increased, while the prevalence of plasmid-borne CRGs has decreased. The study also identified key transmission hubs for various STs, highlighting the importance of monitoring and controlling CREC transmission. The findings underscore the need for comprehensive strategies to address the global challenge of antimicrobial resistance, including the implementation of policies to restrict the use of carbapenem antibiotics and the integration of the "One Health" framework for prevention and control.