PURPOSE: The aim of this systematic review was to document evidence of the association between leisure participation and quality of life (QoL) in children with neurodevelopmental disabilities, and to identify the main factors that further clarify this relationship. METHODS: An electronic search of the literature was conducted using Medline, Embase, PsycInfo, CINAHL, ERIC, OT Seeker, and the Cochrane library using relevant MESH heading and key words. An inductive thematic analysis was used to synthesize main findings from the studies. The mixed methods appraisal tool (MMAT) was used to assess the methodological quality of the included studies. RESULTS: Nineteen studies were included in this systematic review. All 19 studies fulfilled most of the criteria outlined by the MMAT for each study design (quantitative, qualitative, and mixed methods). Mixed methods studies had the lowest MMAT scores. Seven themes were identified that further elucidate the important relationships between leisure participation and QoL: active physical leisure participation and physical well-being; leisure participation and self; leisure participation and emotional well-being; leisure participation and social well-being; leisure participation and cognition; leisure preferences and well-being; and negative aspects of leisure participation. CONCLUSIONS: The use of thematic analysis enabled the synthesis of findings from quantitative, qualitative, and mixed methods study designs. Participating in both naturally occurring, spontaneous forms of leisure activities and participating in more structured types of leisure and therapeutic programs that focus on leisure contribute to improving the QoL of children with neurodevelopmental disabilities. A key aspect to consider is the child’s ability to participate in his/her preferred leisure activities. Environmental adaptations may be required to ensure that the leisure opportunities meet the children’s capabilities and contribute positively to their QoL.