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The Pyrenean-Cantabrian Orogen arose through the collision of the Iberian and Eurasian plates, mostly in Cenozoic times. This orogen comprises two main mountain ranges, the Pyrenees to the east, and the Cantabrian Mountains to the west. To date, the early Alpine tectono-sedimentary phases preserved in the Cantabrian Mountains, of Permian and Triassic age, have been considered independently from the same phases in neighbouring basins of SW Europe, and even from the eastern part of the same orogeny (the Pyrenean orogeny). In consequence, the beginning of the Alpine cycle in the Cantabrian Mountains has been interpreted within a specific geodynamic context, far from the general evolutionary phases of the western Peri-Tethys basins. Through detailed field work, including geological mapping, sedimentology, lithostratigraphy and petrology of volcanic rocks, and new palaeontological data, here we define several new lithostratigraphical formations and five new tectono-sedimentary cycles (TS I-V) for the initial phases of evolution of the Mesozoic Basque-Cantabrian Basin, interrupted by periods of tectonic stability. To complete this information, we include data from an onshore borehole (Villabona Mine) and two offshore boreholes constrained by 2D reflection seismic profiles acquired in the North Iberian continental platform. The main tectono-sedimentary cycles, related to the deposition of five major identified lithostratigraphic units, can be described as follows: TS I (late Gzelian-early Asselian), relating to the late Variscan deformation and preserved in a single outcrop in all the Cantabrian Mountains (San Tirso Formation). This formation is constituted by medium-distal alluvial fan deposits in which humid intervals predominate, forming some thin coal beds. TS II (Asselian-Sakmarian), a post-Variscan extensional phase with associated calc-alkaline magmatism, represented by profuse volcanic and volcanosedimentary intercalations in the early Permian sedimentary basins (Acebal Formation) and small plutons in surrounding areas. TS III (Kungurian), or reactivation of the post-Variscan extension leading to alluvial and lacustrine carbonate sedimentation in arid climate conditions, which do not change during the rest of the Permian and Triassic periods (Sotres Formation). A generalized karstification in the basin represents the end of Permian deposition, followed by an interruption in sedimentation longer than 30 Myr. The Permian tectono-sedimentary cycles (TS II and TS III) are contemporary with Variscan belt collapse and the basins are controlled by extensional reactivation of NE-SW and E-W Variscan structures, and NW-SE late Variscan structures. TS IV (late Anisian–middle Carnian), renewed sedimentation in more extensive basins, precursors of the great Mesozoic Basque-Cantabrian Basin. This cycle is represented by fluvial deposits (Cicera Formation, or Buntsandstein facies), which are interrupted by the first Mesozoic marine ingression (Rueda Formation, or Muschelkalk facies). TS V (Norian-Rhaetian), or shallow marine carbonate deposits (Transición Formation) related to increasingly compartmentalized sub-basins, controlled by normal faults. This final TS is broadly connected with different basins of the western Peri-Tethys domain. The identification of units TS I-V in the Cantabrian Mountains along with the volcanic character of TS II, all indicate the development of a common post-Variscan to early Alpine tectono-sedimentary evolution for the whole Pyrenean-Cantabrian realm. This work was funded by projects CGL2014-52699P and CGL2015-70970-P (Spanish Ministry of Economy and Competitiveness and FEDER Funds of the European Union), as well as projects: >Sistemas Sedimentarios y Variabilidad Climática> (642853) of the CSIC, Basin Analysis (910429), and Palaeoclimatology and Global Change (910198) of the Universidad Complutense de Madrid. The authors thank Luis Villa Iglesias and José Antonio Marín Barcaíztegui (MINERSA GROUP) for providing all the required borehole data from the Villabona Mine (Asturias) and for facilitating access to the mines for sampling. We thank both anonymous referees and Editor Andre Strasser for improving the final version with their comments, and A. Burton for reviewing the English.