The paper presents the results of a comprehensive major element, trace element, and Sr-Nd-Pb-Hf isotopic study of Mid-Tertiary volcanic sequences from the northwestern flood basalt province in Ethiopia. The volcanic rocks studied range in composition from basanites, alkaline basalts, and ankaramites, which form the 1st three sequences at the base associated with basaltic agglomerate (sequence 1, 2 and 3) to transitional and tholeiitic basalts and picrites confined to the upper three sequences (sequences 4, 5 and 6). Sequence 5 is bimodal with intermediate-felsic pyroclastic rocks intercalating the transitional-tholeiitic basalts. There is a good correlation of sequences with geochemical enrichments, such as an increase La/LuN with TiO2, and decrease in Al2O3 and SiO2 towards the base. The smooth increase of La/LuN ratios in lower sequences reflect the general decrease of degree of partial melting that sampled heterogeneous packages of mantle plume materials. In the Sr-Nd isotopic diagram two clusters are formed one with restricted and low- Sr- (0.70356-0.70345) and Nd- (0.51290-0.51284) isotopic compositions, defined by sequence 1, and the other cluster with relatively higher 87Sr/86Sr (0.7052-0.7036) and 143Nd/144Nd (0.51296-0.5127) isotopic compositions defined by samples from sequence 2, and most other sequences with little scatter. The Pb-isotopic compositions vary systematically within each sequence (from base to top), and each sequence clustered systematically in a different Pb–Pb– isotopic space with the highest 206Pb/204Pb (19.10-19.30) and 207Pb/204Pb (15.60-15.65) measured in sequence 1, quite differently from other sequences and from previously reported for northwestern Ethiopian flood basalt province, and the lowest 206Pb/204Pb (18.20-18.56) and 207Pb/204Pb (15.51-15.55) measured in sequence 4. Sequence 2 and 3 lavas display a similar 206Pb/204Pb and 207Pb/204Pb ranges falling between sequence 1 and 4. In contrast, sequence 6 samples displayed towards higher 206Pb/204Pb than sequence 2, 3, and 4, but with lower and higher 207Pb/204Pb than sequence 1 and 5 respectively. The lavas of sequence 1 and 4 have relatively less radiogenic 176Hf/177Hf than other sequences with slight scatter. The systematic geochemical variations in lavas are remarkable and reflects three mantle end component mixing with minimal crustal in put as a fourth component. The enriched sequence 1 has very similar geochemistry to HIMU-type ocean island basalts (OIBs), and this end member ascribed to be the most enriched Afar plume component 1, which is the most enriched Afar Plume component during initial continental break. The second enriched component is defined by sequence 2 and 3 samples and may reflect the second enriched component in Ethiopian flood basalt, previously reported for the high-Ti2 basalts assumed to be the enriched Afar Plume component, whereas the third component is the depleted component defined by sequence 4 partly overlap the range previously reported for low-Ti basalts. Keywords: Flood basalts, Geochemistry, Sr-Nd, Pb-Pb, Hf-Hf isotopes, Afar Plume, Partial melting, Crustal input