Academic collaboration has long been promoted as a vehicle for knowledge creation, capacity building, and institutional strengthening in the Global South. However, the dominant discourse has largely been constructed from a Global North vantage point, reinforcing asymmetrical structures of knowledge production and perpetuating long-standing dependencies. Traditional North–South partnerships, while often beneficial, have tended to reproduce hierarchies in which institutions in the South occupy a subordinate role as recipients of expertise and resources. In light of these imbalances, this chapter critically interrogates the imperatives of academic collaboration in Africa, situating the analysis within broader Global South experiences. South–South collaboration—encompassing partnerships among institutions in Africa, Asia, and Latin America—remains comparatively underdeveloped, not due to lack of relevance, but because of entrenched structural, political, and financial barriers that privilege North–South arrangements. Nevertheless, there is a growing recognition that shared developmental challenges and contextual commonalities among Southern regions may be more effectively addressed through horizontal and mutually reinforcing partnerships. This chapter therefore advances a perspective on research collaboration by introducing conceptual foundations and operational realities in the Global South. It pays particular attention to Africa, where the Africa Charter for Transformative Research Collaborations represents a significant effort to disrupt inherited patterns, foreground equity, and chart new trajectories for sustainable, contextually grounded, and globally relevant scholarly cooperation.