Adults with autism spectrum disorder (ASD) and significant intellectual disability (ID) often have limited speech communication abilities. Abundant research supports use of augmentative and alternative communication (AAC) to enhance skills of children with ASD and ID, but less research has examined efficacy of AAC with non-speaking adults. In this study, three adults with ASD and significant ID were taught basic functional communication using the iPod Touch® with MyTalk Mobile® software within a single-case, multiple-probe across-subjects design. The iPod Touch® taught with most-to-least prompting increased participants’ independent manding, participants were able to discriminate between picture symbols, and participants’ manding generalized to a naturalistic setting with typically available preferred items. Implementation of AAC coincided with increases in speech for one participant. Results illustrate how an applied behavior analysis approach incorporating a speech generating device is effective in teaching communication to adults with ASD and significant ID.