Community Health Centre (CHC) client populations with a history of mental illness or substance use disorders, or both, are not described well in the literature. We identified CHC clients in Ontario with a history of health care related to mental health or substance use disorders, or both, and describe their demographic characteristics, health system use and related health risks in comparison to other people in the province with similar diagnoses who did not use CHC services. We conducted a population-based cohort study using provincial health administrative data among Ontario residents aged 21-105 years with a previously established medical history of a mental illness or substance use disorder, or both. We examined 3 groups: clients of CHC sites that serve at-risk priority populations (PPCHCs) who presented for care at a CHC between Apr. 1, 2014, and Mar. 31, 2015, clients of CHC sites that serve nonpriority populations (NPPCHCs) who presented for care at a CHC over the same period, and a community control group of patients with a history of health care use related to mental illness or substance use disorders, or both, in the 2 years before the index date who were not CHC clients. We used descriptive statistics and multivariable logistic regression to estimate the odds of psychiatric care and emergency department use within 1 year of the index date. Compared to the community control patients (n = 1 673 200), clients of PPCHCs (n = 6575) and NPPCHCs (n = 15 208) were younger, experienced more residential instability and had an increased prevalence of medical comorbidities; they had higher odds of receiving care from a psychiatrist (adjusted odds ratio [OR] 1.26, 95% confidence interval [CI] 1.20-1.33, and 1.47, 95% CI 1.41-1.53, respectively) and visiting an emergency department (adjusted OR 1.15, 95% CI 1.10-1.20, and 1.13, 95% CI 1.09-1.17, respectively) in the 1-year follow-up period. Ontario CHC clients with mental health or substance use disorders had medically complex needs and were intensive users of the health care system. Specific interventions should be developed to better serve this vulnerable population.