Reading comprehension is important to academic success and quality of life. However, evidence suggests that many students with autism spectrum disorders (ASD), even those who read accurately do not have well-developed reading comprehension skills. Collaborative Strategic Reading (CSR) is a fully developed evidence-based instructional approach to reading comprehension with a long history of experimental and quasi-experimental validation. CSR combines strategy instruction with cooperative learning to help struggling readers make meaning out of instructional level text. A modified version, CSR–Lite was adapted for three high school students with ASD who are accessing primarily academic content across the school day. The implemented strategies included previewing, clarifying parts of text that are difficult to comprehend, generating questions, and summarizing. Adaptations for students with ASD included priming, visual support (e.g., pictures, graphic organizers), prompting, and self-monitoring. A multiple-baseline design across three high school students with ASD was employed to examine the effects of implementing CSR-Lite. Challenging behaviors, social interactions, and performance on reading comprehension probes were measured during baseline, intervention, and maintenance conditions. Results indicate an increase in accuracy of responding to reading comprehension probes, a decrease in challenging behavior, and improvement in social interaction in the three participants. Findings from this study suggest that evidence-based reading interventions (e.g., CSR) may be beneficial for students with ASD, when adapted to meet their unique needs. Implications for practitioners and future research are discussed within the context of adapting evidence-based reading comprehension interventions for students with ASD.