Research suggests that challenges associated with raising a child with an Autism Spectrum Disorder (ASD) can increase parents' risk for diminished parenting self-efficacy (PSE) and psychological wellbeing. The present study aimed to explore interrelationships between noteworthy predictors of PSE and parental psychological distress, including parental mastery beliefs and the co-parenting relationship amongst 122 Australian parents of children with autism. Results indicated that greater mastery beliefs and more favourable co-parenting relationships predicted greater PSE, and higher PSE predicted less psychological distress. PSE significantly mediated relationships between mastery beliefs and psychological distress, and between the co-parenting relationship and psychological distress. Findings have implications that can aid professionals to more effectively support parents raising children on the autism spectrum.