Epidemiological evidence suggests that poor physical health and depression are highly co-morbid. To date, however, no study has considered whether depression in parents caring for children with developmental disabilities is partly driven by poor physical health. Using data from the Growing Up in Ireland national cohort study (2006 to date), 627 parents of children with developmental disabilities were compared with 7941 parents of typically developing children on scores from the Centre for Epidemiological Depression Scale, chronic health conditions, socio-demographic and child behavioural characteristics. Having a child with disabilities was associated with a higher risk of depression (odds ratio (OR) = 1.83, 95% confidence interval (CI): 1.43, 2.35) compared to parents of typically developing children. Adjusting for the presence of chronic health conditions accounted for some of this excess risk (OR = 1.77, 95% CI: 1.38, 2.27). The association between having a child with disabilities and increased risk of depression was explained, however, by adjusting for the child problem behaviours (OR = 1.07, 95% CI: 0.81, 1.43). This study has confirmed, in a population-based sample, the high risk of depression in parents caring for children with developmental disabilities after adjusting for the presence of a chronic health condition. Importantly, given that poor mental health in these parents is associated with a battery of negative health and social family outcomes, it is imperative that health professionals pay attention to the mental health needs of these parents.