The worldwide rise of antibiotic-resistant Escherichia coli, a major cause of urinary tract infections (UTIs), has intensified concerns over patient outcomes, illness severity, and healthcare costs. This study investigated the antimicrobial resistance patterns of uropathogenic E. coli (UPEC) isolates, emphasizing the prevalence of extended-spectrum β-lactamase (ESBL) and carbapenemase producers and their associated resistance trends. A prospective study was conducted at BGS Global Institute of Medical Sciences, Bengaluru, from June 2021 to May 2022, involving 226 UPEC isolates. Antimicrobial susceptibility testing revealed high resistance to ciprofloxacin (50.9%), ampicillin (59.6%), and aztreonam (61.5%), while notable susceptibility was observed to fosfomycin (97.5%), amikacin (93.7%), and imipenem (93.4%). ESBL production was confirmed in 36.7% of isolates, and 3.1% were identified as carbapenemase producers. Molecular analysis showed that bla_TEM and bla_CTX genes were associated with ESBL production, while bla_VIM was associated with carbapenemase production. There was no significant correlation between ESBL and carbapenemase expression. The findings highlight the alarming prevalence of multidrug-resistant UPEC and underline the necessity for continuous surveillance of antimicrobial resistance patterns. The preserved activity of fosfomycin, amikacin, and imipenem suggests their continued utility in managing resistant UTIs. Rational antibiotic use and stringent infection control measures remain imperative to curb the further spread of resistant strains.