Musical experiences are ubiquitous in early childhood. Beyond potential benefits of musical activities for young children with typical development, there has long been interest in harnessing music for therapeutic purposes for individuals with autism spectrum disorder (ASD). However, there is debate as to the effectiveness of these approaches and thus a need to identify mechanisms of change (or active ingredients) by which musical experiences may impact social development in young children with ASD. In this review, we introduce the PRESS-Play framework, which conceptualizes musical activities for young children with ASD within an applied behavior analysis framework consistent with the principles of naturalistic developmental behavioral interventions. Specifically, the PRESS-Play framework proposes that musical activities support key elements of evidence-based approaches for social engagement including predictability, reinforcement, emotion regulation, shared attention, and social play context, providing a platform for delivery and receipt of social and behavioral instruction via a transactional, developmental approach. PRESS-Play considers that these factors may impact not only the child with ASD but also their interaction partner, such as a parent or peer, creating contexts conducive for validated social engagement and interaction. These principles point to focused theories of change within a clinical-translational framework in order to experimentally test components of social-musical engagement and conduct rigorous, evidence-based intervention studies.