This study aimed to understand the experiences, barriers, and facilitators of rural general practitioners’ involvement with high-acuity patients. Semi-structured interviews with rural general practitioners in South Australia who had experience delivering high-acuity care were audio-recorded, transcribed verbatim, and analyzed through content and thematic approaches incorporating Potter and Brough’s capacity-building framework. Eighteen interviews were conducted. Barriers identified include the inability to avoid high-acuity work in rural and remote areas, pressure to handle complex presentations, lack of appropriate resources, lack of mental health support for clinicians, and impacts on social life. Enablers included a commitment to community, comradery in rural medicine, training, and experience. We concluded that general practitioners are a vital pillar of rural health service delivery and are inevitably involved in disaster and emergency response. While the involvement of rural general practitioners with high-acuity patients is complex, this study suggested that with the appropriate system, structure and role supports, rural general practitioners could be better empowered to manage high-acuity caseloads locally.