Instruction and support for students with intellectual disability in general education classes should be informed by research-based interventions. In this systematic review, we examined the focus and impact of interventions delivered in inclusive classes to support middle and high school students with intellectual disability. We identified 40 intervention studies involving 177 secondary students with intellectual disability attending a range of core academic and elective classes. These multicomponent interventions fell within five primary categories: systematic instruction, peer support arrangements, self-management strategies, peer-mediated communication interventions, and educational placement changes. Although the overall focus was fairly balanced across academic, social, and behavioral outcomes, each intervention approach prioritized somewhat different dependent measures. Moreover, although the impact of the interventions on most outcomes was positive, the methodological quality of these studies was somewhat varied. We offer recommendations for future research and practice aimed at strengthening the availability and implementation of effective interventions within inclusive secondary school classes.