ImportanceExtended-spectrum β-lactamase (ESBL)–producing Escherichia coli is considered a leading pathogen contributing to the global burden of antimicrobial resistance.ObjectiveTo better understand factors associated with the heterogeneity of community-acquired ESBL-producing E coli urinary tract infections (UTIs) in France.Design, Setting, and ParticipantsThis cross-sectional study performed from January 1 to December 31, 2021, was based on data collected via PRIMO (Surveillance and Prevention of Antimicrobial Resistance in Primary Care and Nursing Homes), a nationwide clinical laboratory surveillance system in France. Strains of E coli isolated from community urine samples from January 1 to December 31, 2019, from 59 administrative departments of metropolitan France were included.Main Outcomes and MeasuresQuasi-Poisson regression models were used to assess the associations between several ecological factors available on government and administration websites between 2010 and 2020 (demographic population structure, living conditions, baseline health care services, antibiotic consumptions, economic indicators, animal farming density, and environmental characteristics) and the number of ESBL-producing E coli strains isolated from urine samples of individuals with community-acquired UTI in 2019.ResultsAmong 444 281 E coli isolates from urine samples tested in 1013 laboratories, the mean prevalence of ESBL-producing E coli was 3.0% (range, 1.4%-8.8%). In an adjusted model, the number of community-acquired ESBL-producing E coli UTIs in each department was positively associated with the percentage of children younger than 5 years (adjusted β1 coefficient, 0.112 [95% CI, 0.040-0.185]; P = .004), overcrowded households (adjusted β1 coefficient, 0.049 [95% CI, 0.034 to 0.062]; P < .001), consumption of fluoroquinolones (adjusted β1 coefficient, 0.002 [95% CI, 0.001-0.002]; P < .001), and tetracyclines (adjusted β1 coefficient, 0.0002 [0.00004 to 0.00039]; P = .02), and poultry density (adjusted β1 coefficient, 0.0001 [95% CI, 0.0001-0.0002]; P < .001). The social deprivation index (adjusted β1 coefficient, −0.115 [95% CI, −0.165 to −0.064]; P < .001) and the proportion of water surface area (adjusted β1 coefficient, −0.052 [−0.081 to −0.024]; P = .001) were negatively associated with a higher number of community-acquired ESBL-producing E coli UTIs.Conclusions and RelevanceThe findings of this cross-sectional study suggest that multiple human health, animal health, and environmental factors are associated with the occurence of community-acquired ESBL E coli UTI. Strategies to mitigate ESBL in the community should follow the One Health approach and address the role played by fluoroquinolones, tetracycline use, poultry density, overcrowded households, and preschool-aged children.