Vocabulary knowledge is critical for accessing content-area information for students with learning disabilities who receive instruction in general education content-area classes. Therefore, the purpose of this study was to examine the effects of a peer-mediated science vocabulary intervention in general education classrooms on academic achievement of seventh-grade students with and without learning disabilities. A quasi-experimental design with multiple pre- and posttest measures was used to determine the effects of the intervention and whether the intervention was differentially effective for students with learning disabilities compared to their nondisabled peers. The study included 8 teacher participants and 675 student participants in 41 classes. The peer-mediated science vocabulary intervention took place two days per week with a third day for weekly assessments. Students learned 8 new science terms per week by working with their partner using a student routine and researcher developed science vocabulary cards. Results indicated that students in the peer-mediated vocabulary intervention condition outperformed students in the non peer-mediated condition on three academic measures including vocabulary assessments, science standards-based assessments, and numerical grades. However, students’ weekly vocabulary growth on science curriculum-based measures was similar for students in both groups. Teachers who implemented the peer-mediated science vocabulary intervention reported overall positive perceptions of the effectiveness and feasibility of the intervention. Students who participated in the peer-mediated science vocabulary intervention indicated they enjoyed working with a peer but reported less favorable opinions regarding the general vocabulary procedures.