Financial challenges, social and material instability, familial problems, living conditions, structural issues, and mental health problems have been shown to contribute to youth homelessness. Based on the paucity of literature on mental illness as a reason for youth homelessness, the current study retrospectively evaluated the association between the timing of homelessness onset (youth versus adult) and mental illness as a reason for homelessness among homeless adults living in homeless shelters and/or receiving services from homeless-serving agencies. Homeless participants (N = 919; 67.3% men) were recruited within two independent studies from Dallas and Oklahoma. Covariate-adjusted logistic regressions were used to measure associations between homelessness onset and mental illness as a reason for current homelessness, history of specific mental illnesses, the historical presence of severe mental illness, and severe mental illness comorbidity. Overall, 29.5% of the sample reported youth-onset homelessness and 24.4% reported mental illness as the reason for current homelessness. Results indicated that mental illness as a reason for current homelessness, history of specific mental illnesses, Schizophrenia/schizoaffective disorder, history of severe mental illness, and severe mental illness comorbidities were each associated with increased odds of youth-onset homelessness. A better understanding of these relationships could inform needs for early interventions and/or better prepare agencies that serve at-risk youth to address precursors to youth homelessness.