The Sesia Zone within the Tertiary arc of the western Alps is a relic of the subducted part of the Adriatic continental margin along the SE border of the Tethyan ocean. The Sesia Zone comprises three basement nappes which individuated during Late Cretaceous (65–80 Ma) subduction to different depths at high‐pressure (HP, blueschist, eclogite facies) conditions (peak pressures of 1.0–1.2, 1.0–1.5, and 1.5–2.0 GPa). The thrusts bounding these nappes developed where the crust was previously thinned during Jurassic rifting. Crustal‐scale shear zones partly overprinted these early thrusts and exhumed coherent slices of crust containing HP rocks. Initial exhumation of the internal part of the accreted margin involved thrusting (D1) and transpressional shearing (D2) along a subvertical, E‐W trending mylonitic shear zone under retrograde blueschist‐ to greenschist‐facies conditions. This exhumation was nearly isothermal to a depth of about 25 km, where the basement nappes were juxtaposed. Subsequent exhumation of these nappes to a common depth of about 15–20 km occurred in the footwall of a greenschist‐facies, top‐SE extensional shear zone (D3) preserved in some of the highest mountain peaks of the Sesia Zone. New Rb‐Sr mineral ages constrain D2 to have occurred at about 60–65 Ma and D3 at about 45–55 Ma. Thus top‐SE extensional exhumation was broadly coeval with Eocene, SE directed subduction of the Liguro‐Piemont oceanic lithosphere beneath the Adriatic margin. Slow cooling and erosional denudation of the Sesia Zone from 45 to 30 Ma occurred in the hanging wall of the Gressoney extensional shear zone (D4), which itself contributed to the exhumation of Eocene HP and ultra‐HP oceanic rocks in its footwall. By 30 Ma, HP rocks of the Sesia Zone were intruded by shallow granitic plutons which were eroded and redeposited within volcanoclastic sediments. Oligo‐Miocene Insubric backfolding and thrusting (D5) only exhumed northeastern parts of the Sesia Zone, where HP metamorphism is absent or was overprinted by Tertiary temperature‐dominated metamorphism. Most exhumation of continental HP rocks in the Sesia Zone therefore preceded Tertiary Alpine collision and coincided with Late Cretaceous to Early Tertiary subduction of the Adriatic and Tethyan lithosphere. The transition from D2 to D3 in the Sesia Zone is interpreted to mark a change from high‐stress, oblique SE directed subduction and accretion of the distal Adriatic continental margin to NW retreating, low‐stress subduction of the Liguro‐Piemont oceanic lithosphere.