The Priest River, Clearwater, Bitterroot, and Anaconda metamorphic core complexes of the northern Rocky Mountains were exhumed in Eocene time by crustal extension, which was linked via dextral displacement on the Lewis and Clark fault zone. Detailed geochronology and thermochronology (U-Pb, ⁴⁰Ar/³⁹Ar, and fission-track) from the Bitterroot complex indicates that extension started at 53 ± 1 Ma and continued until after 40 Ma. New U-Pb zircon and ⁴⁰Ar/³⁹Ar data from the Anaconda complex and published geochronology from the Priest River complex indicate a similar timing for the onset of major extension and exhumation. ⁴⁰Ar/³⁹Ar data from the Clearwater complex, which formed within a relay between strike-slip splays of the Lewis and Clark fault zone, are consistent with exhumation during the same time span. The Lewis and Clark fault zone separates ENE-directed extension in the Priest River complex from ESE-directed extension in the Bitterroot and Anaconda complexes. Large-scale extension was transferred eastward on the south side of this fault zone, where stretching lineations in core complex mylonites are oriented ∼104°–110° and coincide with the general trend of the transcurrent faults. Extension and exhumation of middle crustal rocks along the Lewis and Clark fault zone was concentrated in areas that also experienced voluminous Eocene midcrustal magmatism. Extension was probably initiated by a change in plate boundary conditions combined with the rapid influx of heat from the asthenosphere as a slab window opened beneath the western Cordillera, which led to collapse of the Cordilleran orogenic wedge and widespread early Eocene magmatism.