A child's diagnosis of autism spectrum disorder (ASD) alters family dynamics, heightens marital discord and parenting stress, and may result in parental psychopathology. This may impact the long-term prospects for their children. This study aimed to evaluate the prevalence of depression among parents of autistic children and the factors that predict these conditions. Two hundred and thirty file children were diagnosed with autism and their mothers were enlisted from the Sindh Institute of Physical Medicine & Rehabilitation (SIPM&R), Karachi Sindh Pakistan. Beck Depression Inventory (BDI) and The Childhood Autism Rating Scale (CARS) were used to assess depression and the severity of autism, respectively. The demographic information was composed through a predesigned questionnaire. Data were analysed on SPSS version 20. Descriptive and correlation analyses were used for statistical evaluations. The analysis outcomes exhibited that mainstream mothers hold a master’s degree (54.5%), belong to middle-class families (72.8%), have a nuclear family setup (67.2%), and are housewives (86.8%). The mothers of these children tended to experience moderate depression (65.1%). The severity of an ASD child’s IQ level, adaptive behaviour, and communication characteristics were significantly correlated with depression in the mother (p<0.01). The mothers of children who were receiving treatment had significantly higher BDI scores than those mothers whose children were not under treatment (p<0.01). Hence, offering mental health support to mothers experiencing distress along with researching to explore the root causes of depression is found to be crucial. There is a need to strategise financial and moral support for couples with ASD children to help reduce depression among them.