Computer-assisted instruction (CAI) is growing in popularity and has demonstrated positive effects for students with disabilities, including those with autism spectrum disorder (ASD). In this review, criteria for group experimental and single case studies were used to determine quality (Horner et al., Exceptional Children 71:165–179, 2005; Gersten et al., Exceptional Children 71:149–164, 2005; National Technical Assistance Center on Transition Center 2015). Included studies of high and adequate quality were further analyzed in terms of content, context, and specific instructional practices. Based on the NTACT criteria, this systematic review has established CAI as an evidence-based practice for teaching academics to students with ASD with support from 10 single-case and two group design studies of high or adequate quality. Suggestions for future research and implications for practice are discussed.