Students with learning disabilities (LD) often receive instruction in general education science classrooms. However, little is known about the academic success of students with LD in this setting. As inquiry-based science instruction has become more prominent, research focusing on student learning is needed to explore how such instruction meets students' needs. To address this, a cross-case analysis was conducted. It included six middle school students, each with LD, from a Midwestern city. Each student was enrolled in a general education science class that used inquiry-based instruction. Data sources included student and educator interviews, classroom observations, and student portfolios. Results indicated that most of the students with LD had difficulty acquiring science process knowledge and that students relied on peer supports to facilitate their learning. Findings extend the research on science instruction for students with LD in middle school classrooms using inquiry-based instruction.