Data on the chronicity of mental disorder in children with chronic physical illness (CPI) are limited. We examined the prevalence and predictors of homotypic and heterotypic continuity of mental disorder in children with CPI. A sample of 263 children aged 2-16 years with physician-diagnosed CPI were recruited from outpatient clinics (e.g., dermatology, respiratory) at a Canadian pediatric academic hospital and followed for 24 months. Parent and child-reported mental disorders (mood, anxiety, behavioral, attention-deficit hyperactivity disorder [ADHD]) were assessed using the Mini International Neuropsychiatric Interview for Children and Adolescents at baseline, 6, 12, and 24 months. Marginal regression models were computed to identify clinical, parent, and demographic factors associated with mental comorbidity over time. Mental disorder was observed in 24-27% of children with CPI based on child reports and 35-39% based on parent reports. Parent-reported models revealed significant homotypic continuity for all mental disorders (ORs = 4.2-9.5), and heterotypic continuity between mood and anxiety disorders (OR = 2.2), ADHD and behavioral disorders (OR = 5.1), and behavioral and each mental disorder (ORs = 6.7-8.4). Child-reported models revealed significant homotypic continuity for mood (OR = 8.8) and anxiety disorder (OR = 6.0), and heterotypic continuity between anxiety and mood disorders (OR = 12.4). Child disability (ORs = 1.3-1.5) and parent psychopathology (ORs = 1.2-1.8) were the most consistent predictors of both child- and parent-reported mental disorder over time. Mental comorbidity was prevalent and persistent in children with CPI with homotypic and heterotypic continuity common across informants. Child disability and parent psychopathology may be priority targets within integrated family-centered models of care to prevent mental comorbidity in children with CPI.