Students with intellectual and developmental disabilities (IDD) require intensive supports, including those that target behavior, to make progress on literacy goals. In this study, we investigated whether computer-assisted instruction (CAI) may be one effective method to decrease challenging behavior and increase academic engagement. Participants were three students with IDD (7 to 9 years old) who engaged in challenging behaviors during instruction. We used a single-case alternating treatments design to compare levels of challenging behavior and academic engagement during paper-based and CAI (i.e., tablet computer-based) literacy instruction. Results indicated that CAI was associated with decreased challenging behavior and increased academic engagement for two of three participants. In addition, the CAI condition corresponded with higher scores on academic performance assessments for one participant. Although teacher and student measures of social validity were positive, there was limited evidence that results maintained. These findings are described in relation to their limitations, future directions for research, and impact on practitioners.