The complete genome sequence of uropathogenic *Escherichia coli* strain CFT073 reveals a highly mosaic structure, with only 39.2% of the combined proteins shared among CFT073, enterohemorrhagic *E. coli* EDL933, and laboratory strain MG1655. The pathogen genomes are significantly different from each other, reflecting their distinct disease potential. CFT073 lacks genes for type III secretion systems and phage- and plasmid-encoded toxins found in some diarrheagenic *E. coli*. Instead, it contains genes encoding potential fimbrial adhesins, autotransporters, iron-sequestration systems, and phase-switch recombinases. The large pathogenicity islands of CFT073 differ from those of other well-studied uropathogenic strains, J96 and 536, indicating that extraintestinal pathogenic *E. coli* arose independently from multiple clonal lineages. The genome sequence also highlights the presence of cryptic prophage genomes and the absence of virulence plasmids in CFT073. Codon usage analysis supports the hypothesis that different patterns of codon usage occur between the backbone and island genes, with island genes showing biased use of rare codons. The study underscores the complexity and diversity of *E. coli* evolution, with each strain possessing a unique set of genes that contribute to its specific lifestyle and pathogenic traits.The complete genome sequence of uropathogenic *Escherichia coli* strain CFT073 reveals a highly mosaic structure, with only 39.2% of the combined proteins shared among CFT073, enterohemorrhagic *E. coli* EDL933, and laboratory strain MG1655. The pathogen genomes are significantly different from each other, reflecting their distinct disease potential. CFT073 lacks genes for type III secretion systems and phage- and plasmid-encoded toxins found in some diarrheagenic *E. coli*. Instead, it contains genes encoding potential fimbrial adhesins, autotransporters, iron-sequestration systems, and phase-switch recombinases. The large pathogenicity islands of CFT073 differ from those of other well-studied uropathogenic strains, J96 and 536, indicating that extraintestinal pathogenic *E. coli* arose independently from multiple clonal lineages. The genome sequence also highlights the presence of cryptic prophage genomes and the absence of virulence plasmids in CFT073. Codon usage analysis supports the hypothesis that different patterns of codon usage occur between the backbone and island genes, with island genes showing biased use of rare codons. The study underscores the complexity and diversity of *E. coli* evolution, with each strain possessing a unique set of genes that contribute to its specific lifestyle and pathogenic traits.