Caregiving for children with cerebral palsy (CP) has proved to negatively impact on the physical and psychological well-being of their primary caregivers. The aim of the current study was to examine the overall impact of caregiving for children with CP on the primary caregivers’ health-related quality of life (HRQOL) and family functioning, and to identify potential factors associated with primary caregivers’ HRQOL and family functioning. The cross-sectional study involved a total of 159 primary caregivers of children with CP with a mean age of 42.8 ± 8.4 years. Demographic data and information on the physical and leisure activities of the primary caregivers were collected, and their quality of life (QOL) was measured based on the self-reported Pediatric Quality of Life Inventory Family Impact Module (PedsQL FIM). Primary caregivers in the current study have shown good HRQOL and family functioning, with scores of 82.4 and 85.3 out of 100, respectively. Through multiple linear regression analyses, the mother’s level of education, family monthly income, sleeping problems in children with CP, and the existence of children with other types of disability have been identified as factors contributing to HRQOL and family functioning. The findings help set out the course for stakeholders to establish action to enhance the QOL of primary caregivers.