Over the past decades, there has been a significant increase in the use of computers and mobile devices in schools as part of mathematics instruction for students with learning disabilities (LD). The purpose of this synthesis was to provide a systematic review of the research on the effects of computer-assisted instruction (CAI) for both computers and mobile devices when teaching mathematics to students with LD. Twenty studies met the selection criteria that were published between 1980 and 2017. Findings revealed a wide range of effect sizes across the studies, but in general, the results represent a medium intervention effect and a large maintenance effect of using CAI for students with LD on their mathematics progress. In addition, findings revealed a relationship between the number of evidence-based instructional variables embedded in the CAI instruction and the effect on student performance. Overall, results indicated that well designed CAI with effective instructional variables should be considered as a promising intervention to support mathematics instruction for students with LD.