This study investigated the determinants of quality of life (QOL) of children with cerebral palsy (CP) considering possible variables comprehensively from a biopsychosocial perspective by adopting the International Classification of Functioning, Disability and Health (ICF) and using a CP-specific QOL questionnaire. A total of 167 children with CP (mean age 9.06 years, SD 2.61 years) and their caregivers participated in this study. Children’s QOL was measured by the Cerebral Palsy Quality of Life for Children (CP QOL-Child)-primary caregiver proxy-report form. The potential determinants of QOL were collected based on all ICF dimensions. Results of seven multiple regression models showed that the determinants of QOL in children with CP were multidimensional and biopsychosocial in nature, i.e., encompassing the domains of health condition, body functions and structures, and contextual factors of the ICF. Children’s behavioral and emotional problems as well as caregiver’s psychological and family-related factors were important determinants of QOL in children with CP. Knowledge of the determinants of QOL could serve as a guide in a holistic approach to evaluation and intervention targeted at these determinants to improve the QOL of children with CP.