A comprehensive petrological study carried out on Ethiopian mantle xenoliths entrained in Neogene–Quaternary alkaline lavas overlying the continental flood basalt area (Dedessa River–Wollega region, Injibara-Gojam region) and from the southern Main Ethiopian Rift (Mega-Sidamo region) provides an ideal means to investigate mantle evolution from plume to rift settings. Mantle xenoliths from the plateau area (Injibara, Dedessa River) range in composition from spinel lherzolite to harzburgite and olivine websterite, showing pressure-temperature ( P-T ) equilibrium conditions in the range 1.3–0.9 GPa and 950–1050 °C. These xenoliths show flat chondrite (ch)–normalized bulk-rock rare earth element (REE) patterns, with only few light (L) REE–enriched samples (La N /Yb N up to 7) in the most refractory lithotypes. Clinopyroxene (cpx) REE patterns are mostly LREE depleted (La N /Yb N down to 0.2) or enriched (La N /Yb N up to 4.4). Sr-Nd isotopes of clinopyroxene mainly show compositions approaching the depleted mantle (DM) end member ( 87 Sr/ 86 Sr < 0.7030; 143 Nd/ 144 Nd > 0.5132), or less depleted values ( 87 Sr/ 86 Sr = 0.7033–0.7034; 143 Nd/ 144 Nd = 0.5129–0.5128) displaced toward the enriched mantle components that characterize the Afar plume signature and the related Ethiopian Oligocene continental flood basalts. The 3 He/ 4 He (R a ) values of olivines range from 6.6 to 8.9 R a , overlapping typical depleted mantle values. These characteristics suggest that most xenoliths reflect complex asthenosphere-lithosphere interactions due to refertilization processes by mafic subalkaline melts that infiltrated and reacted with the pristine peridotite parageneses, ultimately leading to the formation of olivine-websterite domains. On the other hand, mantle xenoliths from the southern Main Ethiopian Rift (Mega-Sidamo region) consist of spinel lherzolite to harzburgites showing various degree of deformation and recrystallization, coupled with a wider range of P-T equilibrium conditions, from 1.6 ± 0.4 GPa and 1040 ± 80 °C to 1.0 ± 0.2 GPa and 930 ± 80 °C. Bulk-rock REE patterns show generally flat heavy (H) REEs, ranging from 0.1 chondritic values in harzburgites up to twice chondritic abundances in fertile lherzolites, and are variably enriched in LREE, with La N /Yb N up to 26 in the most refractory lithologies. The constituent clinopyroxenes have flat HREE distributions and La N /Yb N between 0.1 and 76, i.e., in general agreement with the respective bulk-rock chemistry. Clinopyroxenes from lherzolites have 87 Sr/ 86 Sr = 0.7022–0.7031, 143 Nd/ 144 Nd = 0.5130–0.5138, and 206 Pb/ 204 Pb = 18.38–19.34, and clinopyroxenes from harzburgites have 87 Sr/ 86 Sr = 0.7027–0.7033, 143 Nd/ 144 Nd = 0.5128–0.5130, and 206 Pb/ 204 Pb = 18.46–18.52. These range between the DM and high-μ (HIMU) mantle end members. The helium isotopic composition varies between 7.1 and 8.0 R a , comparable to the xenoliths from the plateau area. Regional comparison shows that HIMU-like alkali-silicate melt(s), variably carbonated, were among the most effective metasomatizing agent(s) in mantle sections beneath the southern Main Ethiopian Rift, as well as along the Arabian rifted continental margins and the whole East African Rift system. The different types of metasomatic agents recorded in Ethiopian mantle xenoliths from the continental flood basalt area and the rift systems clearly reflect distinct tectonomagmatic settings, i.e., plume-related subalkaline magmatism and rift-related alkaline volcanism, with the latter extending far beyond the influence of the Afar plume.