Background Children who have been discharged from hospital in sub-Saharan Africa remain at substantial risk of mortality in the post-discharge period. Antimicrobial resistance (AMR) may be an important factor. We sought to determine the prevalence and risk factors associated with AMR in commensal Escherichia coli (E. coli) from Kenyan children at the time of discharge. Methodology/Principle findings Fecal samples were collected from 406 children aged 1–59 months in western Kenya at the time of discharge from hospital and cultured for E. coli. Susceptibility to ampicillin, ceftriaxone, cefotaxime, ceftazidime, cefoxitin, imipenem, ciprofloxacin, gentamicin, combined amoxicillin/clavulanic acid, trimethoprim-sulfamethoxazole, azithromycin, and chloramphenicol was determined by disc diffusion according to guidelines from the Clinical and Laboratory Standards Institute (CLSI). Poisson regression was used to determine associations between participant characteristics and the presence of extended-spectrum beta-lactamases (ESBL) producing E. coli. Non-susceptibility to ampicillin (95%), gentamicin (44%), ceftriaxone (46%), and the presence of ESBL (44%) was high. Receipt of antibiotics during the hospitalization was associated with the presence of ESBL (aPR = 2.23; 95% CI: 1.29–3.83) as was being hospitalized within the prior year (aPR = 1.32 [1.07–1.69]). Open defecation (aPR = 2.02; 95% CI: 1.39–2.94), having a toilet shared with other households (aPR = 1.49; 95% CI: 1.17–1.89), and being female (aPR = 1.42; 95% CI: 1.15–1.76) were associated with carriage of ESBL E. coli Conclusions/Significance AMR is common among isolates of E. coli from children at hospital discharge in Kenya, including nearly half having detectable ESBL.