To identify patient, provider, and delivery system-level factors associated with colorectal cancer (CRC) screening and validate findings across multiple data sets. A concurrent mixed-methods design using electronic health records, provider survey, and provider interview. Eight primary care accountable care organization clinics in Nebraska. Patients' demographic/social characteristics, health utilization behaviors, and perceptions toward CRC screening; provider demographics and practice patterns; and clinics' delivery systems (eg, reminder system). Quantitative (frequencies, logistic regression, and t tests) and qualitative analyses (thematic coding). At the patient level, being 65 years of age and older (odds ratio [OR] = 1.34, P < .001), being non-Hispanic white (OR = 1.93, P < .001), having insurance (OR = 1.90, P = .01), having an annual physical examination (OR = 2.36, P < .001), and having chronic conditions (OR = 1.65 for 1-2 conditions, P < .001) were associated positively with screening, compared with their counterparts. The top 5 patient-level barriers included discomfort/pain of the procedure (60.3%), finance/cost (57.4%), other priority health issues (39.7%), lack of awareness (36.8%), and health literacy (26.5%). At the provider level, being female (OR = 1.88, P < .001), having medical doctor credentials (OR = 3.05, P < .001), and having a daily patient load less than 15 (OR = 1.50, P = .01) were positively related to CRC screening. None of the delivery system factors were significant except the reminder system. Interview data provided in-depth information on how these factors help or hinder CRC screening. Discrepancies in findings were observed in chronic condition, colonoscopy performed by primary doctors, and the clinic-level system factors. This study informs practitioners and policy makers on the effective multilevel strategies to promote CRC screening in primary care accountable care organization or equivalent settings. Some inconsistent findings between data sources require additional prospective cohort studies to validate those identified factors in question. The strategies may include (1) developing programs targeting relatively younger age groups or racial/ethnic minorities, (2) adapting multilevel/multicomponent interventions to address low demands and access of local population, (3) promoting annual physical examination as a cost-effective strategy, and (4) supporting organizational capacity and infrastructure (eg, IT system) to facilitate implementation of evidence-based interventions.