Rural special educators face unique challenges in providing high quality special education services, especially when teaching grade-aligned science content. Computer-assisted instruction (CAI) is one strategy that has the potential to address two major challenges (i.e., a lack of preservice training and limited professional development opportunities) in providing grade-aligned content instruction with fidelity. This study investigated the use of a CAI intervention package to teach three middle school students with autism spectrum disorder and intellectual disability the structure and function of five key elements of an amoeba. Results showed a functional relation between the number of correct responses made during probe sessions and introduction of the CAI intervention. Implications for practice and suggestions for future research are also discussed.