<p>Upper-middle and high income countries employ immigration detention for asylum-seeking/refugee (ASR) children despite documented health risks. We sought to assess the physical and mental health impacts of detention on ASR children in these settings. A systematic review of 15 studies (<i>N</i> = 4,890 children) from 2,512 screened records was undertaken. Relevant databases were searched from 1808 to October 2024 for papers using the search terms ‘unaccompanied/separated/children/minors/adolescents,’ and ‘war/trauma/asylum/refugee,’ and ‘mental illness/ PTSD/depression/ distress, depressive symptoms/ anxiety/physical health/ health/risk factors,’ as well as ‘detention/detain/imprison/incarcerate’. Joanna Briggs Institute tools assessed quality. Strengths and Difficulties Questionnaire (SDQ) data from three studies (<i>n</i> = 239) underwent random-effects meta-analysis as the primary measure of social-emotional and behavioural issues. Duration of detention ranged from 2 weeks to 36 months. Prevalence of PTSD ranged from 6.5% (brief detention &lt; 30 days) to 100% (prolonged detention ≥ 12 months). MDD was reported in 44–95% of children, and suicidal ideation/self-harm in 25–57%. Developmental delays were observed in 75% of children detained ≥ 12 months. Anxiety disorders (45–50%) included separation anxiety and generalised anxiety. The mixed model meta-analysis revealed severe mental health burdens with detained children exhibiting total difficulties scores twice the normative population mean (16.63 vs. 7.1–8.4, 95% CI: 11.19–22.07) with elevated subscale scores for emotional symptoms (5.40 vs. 1.6–2.1, 95% CI: 3.79–7.01), conduct problems (2.93 vs. 1.3–1.6, 95% CI: 1.53–4.32), and peer problems (3.34 vs. 1.4–1.6, 95% CI: 2.17–4.51) (I² &gt;75% for all mental health outcomes). Physical health impacts included malnutrition (24–56%), dental caries (21–54%), vitamin D deficiency (51%), and somatic complaints (e.g., headaches, enuresis). Systemic risk factors—detention duration, family separation, and cumulative trauma—exacerbated harm, with parental mental illness (54%) and dehumanising conditions (e.g., numeric identification) amplifying risks. Comparative data highlight resettled children’s recovery trajectories when provided stability and community support. Most studies were cross-sectional, limiting the ability to assess causality. This review consolidates evidence that establishes a connection between immigration detention and the manifestation of mental disorders, categorising it as an instance of early-life adversity. All fifteen studies identified detrimental consequences, and a meta-analysis of three studies revealed significant emotional distress and behavioural issues. These findings underscore the urgent need for policy reforms to abolish prolonged detention, prioritise family unity, and implement trauma-informed care to mitigate irreversible health consequences for ASR children. Policymakers must recognise these impacts and refrain from detaining and separating children and families.</p><p><b>Systematic review registration:</b> <a href="https://www.crd.york.ac.uk/prospero/">https://www.crd.york.ac.uk/prospero/</a>, registration number CRD42022328867.</p>