This theory of regional cleavages in African politics embeds the behavioral assumptions of microlevel, ethnicity-focused models in a broader spatial, institutional, and temporal frame. A theoretically grounded framework built on economic geography, economic inequalities, and institutions produces general findings about national-level political dynamics in African countries that are close to what classical and mainstream treatments in the comparative politics and comparative political economy literatures would lead us to expect. Leveraging this perspective, this chapter reconsiders questions of economic cleavage, urban–rural politics, institutions, class politics, policy interests, opposition and regional parties, and ethnic identities in African politics. The challenges of territorial politics in regionally divided countries that confront most African countries today are increasingly prominent in non-African, postindustrial countries. This makes research on the politics of spatial inequality in African countries relevant to general understandings of how economic and spatial inequalities may heighten the challenges of national politics. For policy and politics, the analysis lends weight to calls for place-based economic development strategies that are designed to support national cohesion.