Anxiety disorders affect up to 50% of individuals with autism spectrum disorder (ASD) and are significantly impairing to the person affected, as well as to their loved ones. Cognitive-behavioral therapy (CBT) has been established as the gold-standard treatment for anxiety disorders among typically developing youth and adults, and demonstrates similar efficacy among youth with high-functioning autism (HFA). Many CBT interventions utilize a “full-package” treatment approach to treat co-occurring anxiety in youth with ASD. However, these service delivery systems are often therapist-intensive, costly, and impractical, thereby compromising full engagement and treatment adherence. This paper describes the design, rationale, and methodology of a study examining stepped-care CBT for youth with HFA and co-occurring anxiety – a clinical trial examining the efficacy of low-intensity, parent-led CBT as the first line of treatment and utilizing a more intensive, therapist-led intervention for nonresponders. The study will evaluate the potential benefits of stepped-care and parent-led therapist-assisted interventions, predictors of treatment response, and the economic value of using a stepped-care model. Implications for practice will be discussed.