Colonization with antimicrobial-resistant bacteria increases the risk of drug-resistant infections. We identified risk factors potentially associated with human colonization with extended-spectrum cephalosporin-resistant Enterobacterales (ESCrE) in low-income urban and rural communities in Kenya. Fecal specimens, demographic and socioeconomic data were collected cross-sectionally from clustered random samples of respondents in urban (Kibera, Nairobi County) and rural (Asembo, Siaya County) communities between January 2019 and March 2020. Presumptive ESCrE isolates were confirmed and tested for antibiotic susceptibility using the VITEK2 instrument. We used a path analytic model to identify potential risk factors for colonization with ESCrE. Only 1 participant was included per household to minimize household cluster effects. Stool samples from 1148 adults (aged ≥18 years) and 268 children (aged <5 years) were analyzed. The likelihood of colonization increased by 12% with increasing visits to hospitals and clinics. Furthermore, individuals who kept poultry were 57% more likely to be colonized with ESCrE than those who did not. Respondents' sex, age, use of improved toilet facilities, and residence in a rural or urban community were associated with healthcare contact patterns and/or poultry keeping and may indirectly affect ESCrE colonization. Prior antibiotic use was not significantly associated with ESCrE colonization in our analysis. The risk factors associated with ESCrE colonization in communities include healthcare- and community-related factors, indicating that efforts to control antimicrobial resistance in community settings must include community- and hospital-level interventions. © The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.