New structural observations coupled with 15 U/Pb and 24 Ar/Ar new ages from the Karakorum shear zone (KSZ) constrain the timing and slip rate of the right-lateral Karakorum fault zone (KFZ), one of the great continental Asian strike-slip faults. In the Tangtse-Darbuk area, the Tangtse (SW) and Muglib (NE) mylonitic strands of the KSZ frame the less deformed Pangong Range. Inherited U/Pb ages show that granitic protoliths are mostly from the Karakorum and Ladakh batoliths, with a major Miocene melting event lasting from ≥21.5 to 13.5 Ma. Some of the Miocene granitic bodies show structural evidence for intrusion synkinematic to the KSZ. The oldest of these granitoids is 18.8 ± 0.4 Ma old, implying that deformation started prior to ∼19 Ma. Microstructural data show that right-lateral deformation pursued during cooling. Ar/Ar data show that ductile deformation stopped earlier in the Tangtse (∼11 Ma) than in the Muglib strand (∼7 Ma). Deformation ended at ∼11 Ma in the Tangtse strand while it is still active in the Muglib strand, suggesting a progressive localization of deformation. When merged with published observations along the KFZ, these data suggest that the KFZ nucleated in the North Ayilari range at least ∼22 Ma ago. The long-term fault rate is 0.84 to 1.3 cm/yr, considering a total offset of 200 to 240 km. The KSZ collected magma produced within the shear zone and/or deeper in crust for which the producing mechanism stays unclear but was not the lower crustal channel flow.