The seismicity depth distribution in the central and southern East African Rift System (EARS) is investigated using available catalogs from local, regional and global networks. We select well-determined events and make a re-assessment of these catalogs, including a relocation of 40 events and, where necessary, a declustering. About 560 events are finally used for determining foci depth distribution within 6 areas of the EARS. Assuming that short-term deformation expressed by seismicity reflects the long-term mechanical properties of the lithosphere, we build yield strength envelopes from seismicity depth distribution. Using brittle and ductile laws, we predict the strength percentage spaced every 5 km (or sometimes 2 km) in the crust, for a given composition and a specific geotherm, and constrain it with the relative abundance of seismicity. Results of this modeling indicate significant local and regional variations of the thermo-mechanical properties of the lithosphere which are broadly consistent with previous studies based on independent modelings. In order to explain relatively deep earthquakes, a highly resistant, mafic lower crust is generally required. We also find evidence for changes in the strength magnitude and in the depth of the brittle–ductile transitions which are clearly correlated to tectonic provinces, characterized by contrasted thermal gradients and basement types. A clear N–S increase and deepening of the peak strength level is evidenced along the eastern branch of the EARS, following a consistent southward migration of rifting since ~8 Ma. We also detect the presence of a decoupling layer in the Kenya rift, which suggests persisting influences of the deep crustal structures (Archaean and Proterozoic) on the behavior of the extending crust. More generally, our results suggest that seismicity peaks and cut-off depths may provide good proxies for bracketing the brittle–ductile transitions within the continental crust.