Petrological-geochemical comparison of three Mesozoic igneous provinces in South Africa (Karoo Province) and East Antarctica (Queen Maud Land (QML) and Ferrar) confirms the inferred relation of the Ferrar Igneous Province, which is extended for over 3000 km along the margin of the East Antarctic, with the Mesozoic Karoo–Maud plume. Magmatic source in all three regions is characterized by pronounced negative Nb and Ta anomalies. The same features are also typical of magma sources of ancient (Late Proterozoic and Early Paleozoic) dikes within the Mesozoic Ferrar Igneous Province. This compositional similarity is explained by their derivation from a single long-lived source represented by the lithosphere of the East Antarctic Craton. The Ferrar magmatic rocks are also peculiar in the predominant development of low-Ti basalts, which are generated from depleted (through repeated melting) sublithospheric mantle source enriched in potassium during paleosubduction (fluid enrichment). The formation of the Ferrar Igneous Province was related to the lateral spread of the Karoo–Maud plume (as a megaapophysis from the main zone of its manifestation) during melting of metasomatically modified Gondwanian mantle in the vicinity of the Pacific paleosubduction zone. Specific fluid-mediated conditions led to the enrichment of primary melts of the Ferrar Province in large ion lithophile elements such as U, Th, and Rb. Variations of isotope composition of these melts define mixing trends from a mantle source close in composition to the enriched magmas of the Karoo and QML provinces (⁸⁷Sr/⁸⁶Sr: 0.708, ¹⁴³Nd/¹⁴⁴Nd: 0.5122, ²⁰⁶Pb/²⁰⁴Pb: 18.2, ²⁰⁷Pb/²⁰⁴Pb: 15.6, ²⁰⁸Pb/²⁰⁴Pb: 37.6) to a source with elevated ²⁰⁶Pb/²⁰⁴Pb: 20.5, ²⁰⁷Pb/²⁰⁴Pb: 15.7, ²⁰⁸Pb/²⁰⁴Pb: 40.3, ⁸⁷Sr/⁸⁶Sr: 0.716 and lowered ¹⁴³Nd/¹⁴⁴Nd: 0.5124, which was formed owing to the fluid enrichment of mantle in the paleosubduction zone. The isotope composition of ancient magmas located in the Ferrar Igneous Province falls in the composition field of Mesozoic igneous rocks of the Karoo and QML provinces.