Introduction: Parents of children with developmental disabilities, particularly mothers, are likely to suffer from stress. Nevertheless, the association between parenting stress and the type and extent of disability is far from evident. Methods: To examine the relationship between parenting stress, and type and extent of disability, we collected demographic details and the Parenting Stress Scale from 250 mothers of children with a developmental disability attending special-education schools in Karachi. Type and extent of disability were diagnosed by the school's psychologist based on DSM criteria. Adjusted beta-coefficients along with a 95% confidence interval were reported using multiple linear regression. Results: The overall mean parenting stress score among mothers was found to be 43.2 (95% CI: 42.3-44.1). A total of 80 mothers (32%) had a child with Intellectual disability (ID), 60 (24%) with Attention deficit hyperactivity disorder (ADHD), 41 (16%) with Autism, and 69 (28%) with Down syndrome. A large proportion of these children (41%) had mild symptoms and around 26% had severe disability. Multivariable analysis showed that the estimated mean parenting stress score was higher for mothers of children with severe autism ([beta]: 8.09, 95% CI: 3.07, 13.11), severe ID ([beta]: 7.45, 95% CI: 3.71, 11.19) and severe ADHD ([beta]: 7.03, 95% CI: 2.62, 11.44) compared to mothers of children with mild autism, ID, and ADHD. Conclusion: Nurturing a child with special care needs is challenging for mothers. Appropriate clinical services aiming to support parents of children with various disabilities should offer resources to educate and enable mothers to manage their child's disabilities and needs. Tailored parenting interventions must also be introduced to reduce the levels of stress among mothers.