Due to the specific characteristics of its integration into the world economy over the last centuries, sub-Saharan Africa is facing huge spatial imbalances and territorial inequalities. Inherited from the artificial borders shaped by a late European colonization, the political fragmentation of the sub-continent was especially exacerbated by continuing the “rent system” based on the extraction of natural resources. Rent patterns benefited transit capital cities to the detriment of small towns and intermediary cities and resulted in very asymmetric urban structures. Half a century after independence, long-standing poverty and rising inequalities, difficulty of convergence with developed economies, and the challenges related to strong demographic growth, slow structural transformation and pressure on natural resources require strategic choices to be made. While a greater inclusion into the world economy and seizing the opportunities of global value chains are among the policy options, African countries have to tap the full potential of their fast growing domestic markets and to engage in a territorial Reconquista”: focusing on local resources and their adequate management, promoting territorial dynamics through the consolidation of urban-rural linkages and the strengthening of urban networks, and improving their regional integration. Such an evolution implies a reengagement in designing development strategies instead of aligning sectorial policies. It calls for a genuine paradigm shift towards multi-sectorial and place-based approaches, which require the strengthening of a deteriorated knowledge base, capacity building at the local level, and the reconstruction of a strategic vision based on territorial foresight.