The isotopic composition of mafic small-volume intra-plate magmatism constrains the compositions of the sub-continental mantle sources. The Nd, Pb, and Sr isotope signatures of widespread late Mesozoic to Quaternary intra-plate magmatism in NE Africa (Sudan, South Egypt) are surprisingly uniform and indicate the presence of a high-μ (μ = 238U/204Pb) source in the mantle. The rocks are characterized by small ranges in the initial isotopic composition of Nd, Pb, and Sr and most samples fall within ε Nd ca. 3–6, 206Pb/204Pb ca. 19.5–20.5, 207Pb/204Pb ca. 15.63–15.73, 208Pb/204Pb ca. 39–40 and 87Sr/86Sr ca. 0.7028–0.7034. We interpret this reservoir as lithospheric mantle that formed beneath the Pan-African orogens and magmatic arcs from asthenospheric mantle, which was enriched in trace elements (U, Th, and light REE). Combining our new data set with published data of intra-plate magmatic rocks from the Arabian plate indicates two compositionally different domains of lithospheric mantle in NE-Africa–Arabia. The two domains are spatially related to the subdivision of the Pan-African orogen into a western section dominated by reworked cratonic basement (NE-Africa; high-μ lithospheric mantle) and an eastern section dominated by juvenile Pan-African basement (easternmost NE-Africa and Arabia; moderate μ lithospheric mantle). The compositions of the Pan-African lithospheric mantle and the MORB-type mantle of the Red Sea and Gulf of Aden spreading centers could explain the Nd–Pb-Sr isotopic compositions of the most pristine Afar flood basalts in Yemen and Ethiopia by mixtures of the isotopic composition of regional lithospheric and asthenospheric sources.