Rheology of the continental lower crust plays an integral role in governing the style of continental extension. Temperature-dependent creep deformation in the lower crust decreases lithospheric strength and promotes coupling of deformation in the brittle crust and upper mantle; however, few constraints exist concerning the thermal evolution of extending lower crust. Here, we present a high-temperature thermochronological investigation of the Ivrea-Verbano Zone—archetypal continental lower crust that was attenuated during opening of the Alpine Tethys oceanic basin. Rutile U–Pb dates collected from three samples spanning the bottom ～2-km of the crustal section are between ～160 and ～180 Ma, and exhibit near-rim zonations in Zr, Hf, Nb and Ta. Thermal-kinematic modeling of these data, combined with existing rutile U–Pb dates, show that the base of the Ivrea-Verbano Zone experienced heating on two timescales: conductive heating over ～10 Myr, associated with thinning of the lithospheric mantle, and advective heating over <0.1 Myr, associated with high-temperature infiltration of fluids during crustal exhumation. These constraints match the thermal predictions of geodynamic models that predict high-magnitude thinning of lithospheric mantle during the early stages of extension. Conductive heating of lower crust directly preceded mantle exhumation and crustal excision, suggesting that thermal weakening of the lithosphere promotes focusing of extensional strain.