Background Despite the prevalence and mortality associated with colorectal cancer (CRC), 67.4% of US adults aged 50 to 75 years received recommended screening tests in 2016. Objective We created a quality improvement project in resident-run outpatient clinics to increase CRC screening rates to ≥ 50% from 2016 to 2018, with emphasis on vulnerable patient populations. Methods We applied a comprehensive, multidisciplinary approach involving internal medicine and family medicine residents and staff from various hospital network departments, selecting 4 clinics to participate whose screening rates were below our network's average of 41%. Our intervention consisted of a needs assessment, resident-led educational sessions for clinicians, staff, and patients, use of fecal immunochemical tests as a first screening option, and application of care gap analysts at each clinic to answer patients' screening questions and to follow up regarding their screening status. Results We obtained approximately 100 patient surveys from each clinic, a 100% staff completion rate (68 of 68), and a 90% clinician completion rate (85 of 94). Staff and clinician surveys revealed concerns about reducing patient screening fears, inconsistent documentation of screening outcomes, and need for education about CRC prevention, early detection, and screening recommendations. Patient surveys revealed educational deficits and concerns about perceived screening obstacles (eg, transportation and insurance). While CRC screening rates increased across all participating clinics, one clinic experienced an increase from 23% to 48%. Conclusions Our multitargeted approach in primary care residency practices yielded increased CRC screening rates in vulnerable patient populations.