Tackling mental health difficulties in adolescents on the autism spectrum requires a comprehensive prevention approach. A 3-year multisite proof-of-concept longitudinal study implemented an evidence-based multilevel resilience intervention in schools to promote protective factors at the adolescent, parent, and school level. The intervention, consisting of the adolescent, parent and teacher components of the Resourceful Adolescent Program--Autism Spectrum Disorder (RAP-ASD) augmented with the Index for Inclusion, was implemented in 6 secondary schools with 30 adolescents with an autism diagnosis in Grades 7 and 8, 31 parents of 23 of the adolescents, and school staff. The intervention was implemented with good validity and acceptability. Quantitative data from adolescents and parents were analysed using the Reliable Change Index, and qualitative data were analysed using Consensual Qualitative Research. Triangulated quantitative and qualitative outcomes from the majority of adolescents and their parents showed some evidence for promoting resilience for adolescents with a diagnosis or traits of autism, as reflected in reliable improvements in coping self-efficacy and school connectedness, and a reduction in anxiety symptoms and emotional and behavioural difficulties. A reliable improvement in depressive symptoms was more modest and was only achieved by a small minority of adolescents. This multilevel, strength-focused, resilience-building approach represents a promising and sustainable school-based primary prevention program to improve the quality of life for adolescents on the spectrum by promoting their mental health and providing their families with much needed support.