Urinary tract infections (UTIs) are a significant global public health issue, with Escherichia coli (E. coli), specifically uropathogenic E. coli (UPEC), being the predominant causative agent. UTIs affect millions of people annually, with a particularly high prevalence among women, children, the elderly, and individuals with compromised immunity or structural abnormalities of the urinary tract. UPEC has evolved a suite of specialized virulence factors like adhesins, flagella, capsular polysaccharides, lipopolysaccharide (LPS), outer membrane vesicles (OMVs), toxins, iron acquisition systems, autotransporters (ATs), and unique proteins such as TcpC and OmpT, that facilitate colonization, immune evasion, and disease progression. These factors enable the pathogen to cause both uncomplicated infections, such as cystitis, and more severe outcomes, including pyelonephritis and, in some cases, renal failure. The host defends against infection through mechanisms such as urine flow, urothelial shedding, cytokine release, antimicrobial peptides, and adaptive immunity. Despite advancements in medical care, the burden of UTIs remains high, underscoring the need for continued research into their pathogenesis and prevention.