Abstract: Theoretical Background: The Strengths and Difficulties Questionnaire (SDQ) is often used for screening of psychological problems in children with chronic physical health conditions (CPHC). Objective: The present meta-analysis tested (a) whether the SDQ scores of young people with CPHC show elevated psychological symptoms and lower prosocial behavior compared with healthy peers or test norms, (b) which conditions are associated with the strongest increase in symptoms, and (c) whether results vary by sample and study characteristics. Method: Studies that compared SDQ scores between young people with CPHC and healthy peers or test norms or that provided sufficient information for a comparison with established normative data or sociodemographically equivalent healthy groups from that country, and if studies were published or made available online before July, 2023, were included in the meta-analysis. Study quality was evaluated with the Mixed Methods Appraisal Tool. A systematic search in the electronic databases Medline, PsycINFO, PSYNDEX, Web of Science, and the SDQ database resulted in 605 studies of 217,440 children and adolescents with CPHC that were included in random-effects meta-analyses. Results: There were, on average, small-to-moderate elevations in total difficulties (parent/self-report: g = .52/.31) and the four problem scales as well as slight reductions in parent reports on prosocial behavior ( g = -.17). Elevations in parent- and self-reports on emotional symptoms ( g = .48/.31) and peer problems ( g = .43/.26) were significantly stronger than elevations in conduct problems ( g = .30/.10) and hyperactivity–inattention ( g = .33/.13). In addition, children with cerebral palsy (parent/self-report of total problems: g = .82/.66), chronic fatigue syndrome ( g = .82/.66), and epilepsy ( g = .95/.40) showed above-average elevations in psychological symptoms. Stronger effect sizes were found, among others, in older children and in the case of a later age at onset. Direct comparisons of the results of published and unpublished studies on self-rated SDQ found some evidence for a possible publication bias, while results of published and unpublished studies did not vary when parent ratings were used. With regard to limitations, only few studies were available on teacher ratings and from non-Western countries. Illness-specific analyses were impossible for rarely assessed conditions, such as cystic fibrosis and spina bifida. Discussion and Conclusion: It is concluded that children with epilepsy, cerebral palsy, chronic fatigue syndrome, and other conditions affecting the brain should be, in particular, screened for psychological problems. Symptom overlap of some CPHC with the Emotional Symptoms scale has to be considered when interpreting the data.