We investigate the along‐axis variations in architecture, segmentation, and evolution of the Main Ethiopian Rift (MER), East Africa, and relate these characteristics to the regional geology, lithospheric structure, and surface processes. We first illustrate significant along‐axis variations in basin architecture through analysis of simplified geological cross sections in different rift sectors. We then integrate this information with a new analysis of Ethiopian topography and hydrography to illustrate how rift architecture (basin symmetry/asymmetry) is reflected in the margin topography and has been likely amplified by a positive feedback between tectonics (flexural uplift) and surface processes (fluvial erosion and unloading). This analysis shows that ~70% of the 500 km long MER is asymmetric, with most of the asymmetric rift sectors being characterized by a master fault system on the eastern margin. We finally relate rift architecture and segmentation to the regional geology and geophysical constraints on the lithosphere. We provide strong evidence that rift architecture is controlled by the contrasting nature of the lithosphere beneath the homogeneous, strong Somalian Plateau and the weaker, more heterogeneous Ethiopian Plateau, differences originating from the presence of pre‐rift zones of weakness on the Ethiopian Plateau and likely amplified by surface processes. The data provided by this integrated analysis suggest that asymmetric rifts may directly progress to focused axial tectonic‐magmatic activity, without transitioning into a symmetric rifting stage. These observations have important implications for the asymmetry of continental rifts and conjugate passive margins worldwide.