Autism spectrum disorder is characterized by impaired social communication and interaction. As a neurodevelopmental disorder typically diagnosed during childhood, diagnosis in adulthood is preceded by a resource-heavy clinical assessment period. The ongoing developments in digital phenotyping give rise to novel opportunities within the screening and diagnostic process. Our aim was to quantify multiple non-verbal social interaction characteristics in autism and build diagnostic classification models independent of clinical ratings. We analyzed videos of naturalistic social interactions in a sample including 28 autistic and 60 non-autistic adults paired in dyads and engaging in two conversational tasks. We used existing open-source computer vision algorithms for objective annotation to extract information based on the synchrony of movement and facial expression. These were subsequently used as features in a support vector machine learning model to predict whether an individual was part of an autistic or non-autistic interaction dyad. The two prediction models based on reciprocal adaptation in facial movements, as well as individual amounts of head and body motion and facial expressiveness showed the highest precision (balanced accuracies: 79.5% and 68.8%, respectively), followed by models based on reciprocal coordination of head (balanced accuracy: 62.1%) and body (balanced accuracy: 56.7%) motion, as well as intrapersonal coordination processes (balanced accuracy: 44.2%). Combinations of these models did not increase overall predictive performance. Our work highlights the distinctive nature of non-verbal behavior in autism and its utility for digital phenotyping-based classification. Future research needs to both explore the performance of different prediction algorithms to reveal underlying mechanisms and interactions, as well as investigate the prospective generalizability and robustness of these algorithms in routine clinical care.© 2024. The Author(s).