Structural style along the active, NW-striking, right-slip Karakoram fault in western Tibet ranges from transpression in the north (37° to 34°N) to transtension in the south (34° to 32°N). This transition in structural style occurs at a 27-km-wide bend in the fault. Our new neotectonic mapping has documented the long-asserted structural linkage between the ENE-striking Gozha–Longmu Co fault system and the similarly oriented active, left-slip Altyn Tagh fault to the northeast. This mapping also indicated that the restraining bend in the Karakoram fault is located where this fault intersects the Gozha–Longmu Co extension of the Altyn Tagh fault to the west. Additional observations from remotely sensed imagery suggest that the total left-separation along the Gozha–Longmu Co fault system is 25–32 km. We use the new neotectonic mapping and published slip rates to develop a simple kinematic model for the main active faults in western Tibet to explore the genetic relationship between slip along the Gozha–Longmu Co fault system and the geometric and kinematic evolution of the Karakoram fault. This model combines published geodetic and Quaternary slip rates with the known fault geometries and demonstrates that the transition from transpression to transtension along the Karakoram fault can be explained by differential motions between the NW Himalaya, the Tianshuihai terrane, and the Tibetan Plateau. These motions produce bending and transtension along the central and southern Karakoram, respectively, and movement of the Tibetan Plateau at a rate of 6–13 mm/yr toward the east-southeast relative to the Pamirs. We also find that the Gozha–Longmu Co fault system likely initiated between 10 and 3 Ma to accumulate 25–32 km of total left separation. We suggest that the Gozha–Longmu Co fault system formed during late Miocene to Pliocene structural reorganization of the southwestern Altyn Tagh and southern Karakoram fault systems to allow eastward migration of the Tibetan Plateau and northward migration of the Pamir syntaxis.