Ambrym Island, located in the Vanuatu Island arc (Southwest Pacific), is a mainly basaltic volcano active since at least 0.1 Ma that host a 12-13 km wide summit caldera since ~2000 years related in part to a paroxysmal eruption recorded by the Ambrym Pyroclastic Series (APS). Remnants of an older volcanic edifice subsists in the northern part of the island. Calc-alkaline lavas with variable potassium enrichments relative to similar silica content (ranging from basalt to dacite) has erupted throughout the Ambrym edification. A new geochemical study including Sr, Nd, Pb, and Hf isotopic compositions of 20 lavas is presented in this paper, with a focus on each K magmatic series recorded during the eruptive history of Ambrym Island. All Ambrym lavas show a typical arc magma signature in terms of trace element content. Compared to the old medium-K series, the more recent high-K series have similar Sr and Pb isotopic ratios, but lower 143 Nd/ 144 Nd (~0.51291 vs. ~0.51295), 176 Hf/ 177 Hf ratios (~0.28312 vs. ~0.28315), Ba/Th (270 vs. 320) and higher Nb/Yb (1.3 vs. 0.8), La/Sm (~2.7 vs. ~1.8), La/Yb (~5 vs. ~3) ratios. Higher Th/Nb (~0.6) and low Nd, Hf isotopic radiogenic compositions compared to N-MORB suggest the contribution (<2%) of subducted sediment melts to the mantle source of Ambrym lavas. Most of the geochemical features of both magma series could be explain by the involvement of two distinct mantle sources (with different pre-existing enrichments) metasomatized with different slab derived fluids and sediment melts. In addition, high-K series seems to be derived from lower extent of partial melting (8-13 vs. 10-22%), based on their Nb, Zr, La, Sm content. The recent regional rifting along fractures oriented N100° in the south of the old edifice allows an easier (medium-K series) and a new (high-K series) access for magmas and led to the edification of the main cone. Both magma series were likely stored in separate shallow depth reservoirs and participate to a giant eruption that resulted to the enlargement of a pre-existing hawaiian-type caldera topping a shield volcano and the deposit of the mainly mafic Ambrym Pyroclastic Series. Since that time, there is no evidences for an activity from the old magma chamber in the north, as only high-K magmas are now emitted all along the N100° rift zone. This highlights the strong tectonic control on the volcanism at Ambrym Island.