The Marañón Valley, located in the Eastern Cordillera of the northern Peruvian Andes, represents a 160-km-long section of the continental margin that was mainly active during the Paleozoic. A combination of whole rock geochemistry, and U-Pb, O and Hf isotope microanalysis of zircon on selected igneous rocks, reveals the timing and magmatic source variations along and across-strike of the Paleozoic proto-Andean margin. The igneous rocks exhibit a typical arc-related continental margin signature, with strong enrichment in LILE (e.g., Cs, Rb and Th), depletion of HFSE (e.g., Nb) and a negative Ti anomaly. The overlapping Hf-O isotopic compositions, together with similar inherited zircon ages, are consistent with the Lavasen Volcanics, the Esperanza Subvolcanic Complex and the Pataz Batholith sharing the same crustal source components, in about the same proportion. A genetic relationship is further supported by the strong depletion in Sr, Nb, Ta, Ti and Eu in the subvolcanic and volcanic rocks from the Esperanza Subvolcanic Complex and Lavasen Volcanics compared to the intrusive rocks from the Pataz Batholith, which is consistent with evolution of the erupted magmas by fractional crystallization. The new zircon U-Pb (LA-ICP-MS) age determinations, in combination with previously published geochronological data, suggest that the Pataz Batholith, the Esperanza Subvolcanic Complex and the Lavasen Volcanics were emplaced contemporaneously between ca. 342 Ma and 332 Ma. The new Mississippian U-Pb (zircon U-Pb LA-ICP-MS) age determination for the Lavador Pluton (336–332 Ma) and the Callangate-Enaben Pluton (341–337 Ma) suggest that magmatism was coeval with the emplacement of the Pataz Batholith. The Lavador Pluton is aligned with the main N-NW trend of the Pataz Batholith, and shares a similar range of Hf-O isotopic values (i.e., ε Hf (t) values from −5.3 to −1.3 and δ 18 O values from 6.4 to 7.1‰), and is therefore believed to represent a northern extension of the Pataz Batholith. The isotopic geochemistry and lithogeochemistry record in the Marañón Valley illustrates the regional scale tectonic switches that occurred during arc formation, from syn-collisional and compression in the Pataz-Parcoy district between ca. 342 Ma and 332 Ma, to post-collisional and extensional in the Montañitas district between ca. 332 Ma and 319 Ma. The delineation of the timing and location of tectonic regime switches in the Marañón Valley may provide a basis for future mineral exploration.