Background: A lack of specialists, and insufficient infrastructure and funding to scale early interventions for autism spectrum disorder (ASD) characterize low-resource settings. Integration of early intervention methods that utilize non-specialists, and involve caregivers, into existing systems of care, offers the best hope to address such unmet needs. In South Africa, a caregiver coaching intervention, informed by principles of the Early Start Denver Model (ESDM) was adapted for delivery by non-specialist Early Childhood Development (ECD) practitioners. This study explored perceived barriers and facilitators to sustainable implementation of this approach. Methods: Nine stakeholders including caregivers, ECD practitioners, ECD school supervisors, and certified South African ESDM therapists involved in intervention implementation were purposively sampled, and individual in-depth interviews were conducted. Interviews were transcribed verbatim and thematically analyzed. Results: Implementation facilitators included: ECD practitioner ASD knowledge and ongoing supervision; a positive coaching experience; and clear illustration of intervention concepts. Implementation barriers included: complexity of some intervention and coaching concepts; logistical challenges such as time constraints and internet access; and mismatch between video content and the South African context. Facilitators to sustain the intervention included perceived positive child and caregiver outcomes; and ongoing supervision. Barriers to sustain the intervention included socioeconomic contextual factors. Conclusions: In spite of the potential for positive child and caregiver outcomes from caregiver coaching, broader contextual and system-level issues such as poverty, the need for ongoing supervision, and access to local coaching materials in South African languages, may challenge sustainable implementation. Findings from this study will inform tailoring of the intervention training and supervision approach for next step evaluation.