This article analyses the shifting rationales for scientific collaboration in the work of the United Nations Economic, Scientific and Cultural Organization (UNESCO) in the science sector in Africa from the late colonial period through to the era of capacity building. Focusing on the late colonial period and the post-independence decades of “national science” in Africa, it analyses UNESCO’s role in science policy, engineering training, and natural resources research. It demonstrates that in the era of national science UNESCO’s activities were couched in the language of independence: developing capacities in the sciences was regarded as the key to obtaining “scientific independence” to match the recently obtained political independence. This marked a significant change from the 1950s when UNESCO based its operations in Africa on collaborations with the European colonial powers. The article argues that the link between scientific independence and political self-determination gave way as UNESCO rebranded scientific capacity-building activities as efforts in the pursuit of an unclearly-defined common good.