Robots have the potential to facilitate future therapies for children on the autism spectrum. However, existing robots are limited in their ability to automatically perceive and respond to human affect, which is necessary for establishing and maintaining engaging interactions. Their inference challenge is made even harder by the fact that many individuals with autism have atypical and unusually diverse styles of expressing their affective-cognitive states. To tackle the heterogeneity in children with autism, we used the latest advances in deep learning to formulate a personalized machine learning (ML) framework for automatic perception of the children’s affective states and engagement during robot-assisted autism therapy. Instead of using the traditional one-size-fits-all ML approach, we personalized our framework to each child using their contextual information (demographics and behavioral assessment scores) and individual characteristics. We evaluated this framework on a multimodal (audio, video, and autonomic physiology) data set of 35 children (ages 3 to 13) with autism, from two cultures (Asia and Europe), and achieved an average agreement (intraclass correlation) of ~60% with human experts in the estimation of affect and engagement, also outperforming nonpersonalized ML solutions. These results demonstrate the feasibility of robot perception of affect and engagement in children with autism and have implications for the design of future autism therapies.Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.