Despite the high comorbidity, surprisingly little is known about the clinical features, treatment prognosis, and treatment mediators for youth with Obsessive–Compulsive Disorder (OCD) and Autism Spectrum Disorder (ASD). This study, the largest to date, compared 172 young people with OCD and ASD (OCD + ASD) to 447 without ASD (OCD) on clinical characteristics, finding those with OCD + ASD were more likely to endorse poorer insight into their OCD, have greater global functional impairment, greater levels of concurrent psychopathology, higher levels of family accommodation and to be on medication. Treatment outcomes following a course of Cognitive Behaviour Therapy with or without medication were explored for a subgroup; 100 young people with OCD + ASD and 223 with OCD. Whilst both groups benefitted from treatment, the OCD + ASD group had significantly poorer treatment outcomes. Greater global functional impairment and being on medication mediated the between-group difference in outcomes. Further research and treatment refinements are needed to improve outcomes for youth with OCD + ASD.