We examined the peer interactions and academic engagement of 23 middle and high school students with developmental disabilities within inclusive academic and elective classrooms. The extent to which students with and without disabilities interacted socially was highly variable and influenced by instructional format, the proximity of general and special educators, and curricular area. Peer interactions occurred more often within small group instructional formats, when students were not receiving direct support from a paraprofessional or special educator, and in elective courses. Academic engagement also varied, with higher levels evidenced during one-to-one or small group instruction and when in proximity of general or special educators. Implications for designing effective support strategies for students with autism and/or intellectual disability within general education classrooms are discussed.