By global standards, the prevalence of community-onset expanded-spectrum- cephalosporin-resistant (ESC-R) Escherichia coli remains low in Australia and New Zealand. Of concern, our countries are in a unique position, with high extramural resistance pressure from close population and trade links to Asia-Pacific neighbors with high ESC-R E. coli rates. We aimed to characterize the risks and dynamics of community-onset ESC-R E. coli infection in our low-prevalence region. A case-control methodology was used. Patients with ESC-R E. coli or ESC-susceptible E. coli isolated from blood or urine were recruited at six geographically dispersed tertiary care hospitals in Australia and New Zealand. Epidemiological data were prospectively collected, and bacteria were retained for analysis. In total, 182 patients (91 cases and 91 controls) were recruited. Multivariate logistic regression identified risk factors for ESC-R among E. coli strains, including birth on the Indian subcontinent (odds ratio [OR] = 11.13, 95% confidence interval [95% CI] = 2.17 to 56.98, P = 0.003), urinary tract infection in the past year (per-infection OR = 1.430, 95% CI = 1.13 to 1.82, P = 0.003), travel to southeast Asia, China, the Indian subcontinent, Africa, and the Middle East (OR = 3.089, 95% CI = 1.29 to 7.38, P = 0.011), prior exposure to trimethoprim with or without sulfamethoxazole and with or without an expanded-spectrum cephalosporin (OR = 3.665, 95% CI = 1.30 to 10.35, P = 0.014), and health care exposure in the previous 6 months (OR = 3.16, 95% CI = 1.54 to 6.46, P = 0.02). Among our ESC-R E. coli strains, the blaCTX-M ESBLs were dominant (83% of ESC-R E. coli strains), and the worldwide pandemic ST-131 clone was frequent (45% of ESC-R E. coli strains). In our low-prevalence setting, ESC-R among community-onset E. coli strains may be associated with both "export" from health care facilities into the community and direct "import" into the community from high-prevalence regions.