Using Ghana as a case study, this chapter proposes a conceptual framework positioning Generative Artificial Intelligence (GenAI) as a catalyst for transforming entrenched teacher education systems in the Global South. For decades, teacher preparation has been dominated by content-heavy instruction, a “content refuge” that masks persistent deficits in practical training, resource provision, and sustained professional development. The integration of GenAI offers the potential to strengthen content mastery to the extent that such avoidance strategies become untenable, compelling stakeholders, including lecturers, policy makers, and educational institutions, to confront their long-neglected responsibilities in delivering high-quality teacher education. The framework identifies eight interrelated domains through which GenAI could drive systemic change toward this goal: strengthening pedagogical modeling; improving resource acquisition; enhancing performance-based assessment; reducing resistance to change; advancing digital literacy; fostering critical thinking; promoting sustained professional development; and encouraging collaborative learning. If adopted strategically in teacher education, GenAI can help to achieve what decades of reform have failed to deliver due to implementation infidelity; producing teachers with demonstrable competencies who, in turn, will prepare students for the demands of the future workforce, close skills gaps, and reduce unemployment. These latent potentials, however, require intentional and well-structured integration of GenAI into teacher education systems. Future research should empirically evaluate GenAI’s impact within each domain of the framework to generate context-specific evidence that can guide sustainable, equitable, and scalable integration across the Global South.