The Mo-Cu-W Azegour skarn, located in the High-Atlas in Morocco, is associated with a Late Hercynian alkaline granitic intrusion. Here the origin of the mineralisation via Re-Os geochronology and using Mo, S and Pb isotopes is discussed. The age of mineralisation defined by Re-Os molybdenite geochronology is 276 ± 1.2 Ma for the Azegour mine, and 267 ± 1.2 for the Tizgui deposit suggesting for multiple mineralisation events associated with the Hercynian alkaline granitic intrusion. The δ98MoNIST of molybdenite range from −0.60‰ to 0.42‰ (n = 26) for the Azegour mine and from 0.08‰ to 0.40‰ (n = 2) for the Tizgui mine. Variations of the δ98MoNIST occur either at the deposit scale with a difference of about 0.72‰, and at the sample scale (few cm), which exhibits a difference of up to 0.40‰. A multi-phased mineralisation is proposed as the main processes explaining the variation in the δ98MoNIST values although the influence of a Rayleigh fractionation process cannot be precluded. The high δ34S values determined from molybdenite, pyrrhotite, and chalcopyrite (8–14.7‰) suggest a sedimentary origin for sulphur from the Cambrian sedimentary country rocks. Whereas, the initial 206Pb/204Pb compositions of common lead (18.08–18.30) for chalcopyrite and pyrrhotite imply a strong contribution of lead from the host volcano-sedimentary units.