Increasing numbers of students with Autism Spectrum Disorder (ASD) are attending mainstream schools. Nonetheless, concerns about their emotional well-being and mental health in these settings have also been raised. This study sought to compare caregiver-reported anxiety and other emotional and behavioural problems in youth with ASD attending mainstream or specialist schools. Caregivers of 27 youth with ASD in mainstream schools (age 10.91 ± 3.44 years) and 69 youth with ASD in special schools (age 10.93 ± 2.81 years) matched for gender, age, adaptive functioning and autism symptom severity scores participated. Caregivers completed the Spence Children’s Anxiety Scale–Parent, a measure of adaptive functioning, and a checklist of other emotional and behavioral difficulties. Students with ASD attending mainstream schools experienced higher levels of social anxiety symptoms compared to their specialist school counterparts. No other statistically significant differences were found in other aspects of emotional and behavioural functioning examined, but some differences emerged in item-level analyses. Uncertainties in navigating more complex social environments and increased social relating difficulties in mainstream schools are discussed as probable environmental triggers for increased social phobia related symptomatology, although other explanations for this small effect size difference are also considered. Limitations of the present study and recommendations for future research focusing on exploring environmental socio-ecological factors influencing anxiety and mental health in young people with ASD are also discussed.