Infections due to Escherichia coli producing extended-spectrum beta-lactamase (ESBL) or CMY-type beta-lactamase (CMY) are increasingly observed in non-hospitalized patients. The origin of these organisms is uncertain, but retail meat contaminated with E. coli may be a source. In the present study, clinical information and strains collected from patients infected or colonized with ESBL-producing and CMY-producing E. coli at hospitals in Pittsburgh, USA and Seville, Spain were investigated. Retail meat purchased in these cities was also studied for the presence of these organisms. Twenty-five and 79 clinical cases with ESBL-producing E. coli and 22 cases and one case with CMY-producing E. coli were identified in Pittsburgh and Seville, respectively. Among them all, community-acquired and healthcare-associated cases together constituted 60% of the cases in Pittsburgh and 73% in Seville. Community-acquired cases were more common in Seville than in Pittsburgh (49% vs. 13%; p <0.001). ESBL-producing and CMY-producing E. coli isolates were commonly recovered from the local retail meat. In particular, 67% (8/12) of retail chickens in Seville and 85% (17/20) of those in Pittsburgh contained ESBL-producing and CMY-producing E. coli isolates, respectively. Among the ESBL-producing isolates, CTX-M and SHV were the most common ESBL types in both clinical and meat isolates. Approximately half of the ESBL-producing and CMY-producing E. coli isolates from meat belonged to phylogenetic groups associated with virulent extra-intestinal infections in humans. Community and healthcare environments are now significant reservoirs of ESBL-producing and CMY-producing E. coli. Retail meat is a potential source of these organisms.