The heterogeneous continental lithosphere of Europe inherits billion of years of tectonic evolution, mineral transformation and magmatic addition. Though there is now an extensive body of studies on the long-term geological, geochronological and geochemical evolution of the continental crust and lithospheric mantle available in Europe, yet this knowledge has not been linked to the understanding of tectonic evolution of Cenozoic Alpine mountain building. In this aim, we review geophysical, geological, petrographical, geochemical, and thermochronological constraints to infer a kinematically coherent time-integrated tectonic model for the evolution of mountain building in Western Europe, along a 4000 km long lithospheric transect from Africa to the East European Craton. We show that the key drivers of plate-scale processes related to Alpine orogenic and topographic evolution reflect three main ingredients : 1) a protracted magmatic and tectono-thermal transformation of Africa (Gondwana) and North Europea (Baltica) cratonic mantle lithosphere since the Neoproterozoic, 2) an overall limited Mesozoic Tethyan extension of the weak Variscan lithosphere characterized by the lack of wide, thermally relaxed, oceanic lithosphere, 3) a relatively slow Cenozoic convergence between Africa and Europe, preserving initial stages of distributed tectonic inversion of rifted continental blocks throughout Europe, and partial subduction and delamination in the Mediterranean region of the most evolved lithospheric domains.