Cognitive behavioral therapy is a widely studied and commonly used psychosocial intervention for treating emotional problems in individuals with autism. To date, most studies of cognitive behavioral therapy and autism have focused on efficacy. Effectiveness trials, by contrast, measure whether an intervention produces particular results under “real-world” clinical conditions. We conducted a systematic review of cognitive behavioral therapy interventions targeting affective disorders among youth with autism and (a) classified studies as either efficacy or effectiveness trials and (b) coded how the effectiveness trials reflect the implementation characteristics outlined in the Framework of Dissemination in Health Services Intervention Research. The systematic search yielded 2959 articles, with 33 studies meeting inclusion criteria. Thirteen studies were categorized as effectiveness and 20 as efficacy. We discuss how the effectiveness studies considered elements of the implementation framework and provide recommendations for future studies, including greater consideration and measurement of adoption and sustainability processes, as well as organizational- and systemlevel outcomes. Results shed light on our understanding of the effectiveness of cognitive behavioral therapy in routine clinical practice, how an implementation framework can be used to guide and improve effectiveness studies, and identify barriers, facilitators, and gaps in the implementation process.