Abstract Magmatic arcs associated with subduction zones are the dominant active locus of continental crust formation, and evolve in space and time towards magmatic compositions comparable to that of continental crust. Accordingly, the secular evolution of magmatic arcs is crucial to the understanding of crust formation processes. In this paper we present the first comprehensive U–Pb, Hf, Nd and Sr isotopic dataset documenting c. 120 myr of magmatic evolution in the Kohistan-Ladakh paleo-island arc. We found a long-term magmatic evolution that is controlled by the overall geodynamic of the Neo-Tethys realm. Apart from the post-collisionnal melts, the intra-oceanic history of the arc shows two main episodes (150–80 Ma and 80–50 Ma) of distinct geochemical signatures involving the slab and the sub-arc mantle components that are intimately linked to the slab dynamics.