The magmatic history of the Pelagonian Zone, in northern Greece, is constrained with secondary ion mass spectrometer (SIMS) U-Pb dating on zircons of various granitoids whose structural positions were defined with respect to the regional main foliation. Ages pertain to four groups: (i) Mesoproterozoic (circa 1430 Ma) crystallization of granites inferred from inherited magmatic zircon cores that have been partially molten during the (ii) Neoproterozoic at circa 685 Ma (metamorphic zircon rims) and subsequently intruded by a Neoproterozoic leucogranite (circa 600 Ma). (iii) Late- or post-Variscan calc-alkaline granitoids (315–301 Ma) were in turn intruded by a subvolcanic dike at about 280 Ma. In the Early Permian the εNd(t) in magmas decreased from −7.3 to −1.3, hinting to mantle-derived melts produced during extension. Rifting is further heralded by two acidic and one mafic dike containing Lower-Middle Triassic zircons (246–242 Ma). (iv) Early Cretaceous anatectic melts at 117 ± 8 Ma formed during regional metamorphism. This age is the first report of in situ anatexis in the Pelagonian Zone. Cretaceous anatexis developed during the Mesozoic collision of Pelagonia with the Eurasian margin. Major- and trace-element geochemistry of amphibolites further attests for the complex pre-Alpine tectonic history with Neoproterozoic calc-alkaline and back-arc geochemical signature and Triassic alkali-magmatism.