The Thakkhola graben is one of many north-trending rifts that define the Neogene structural pattern of the southern Tibetan Plateau. Lying at the southern margin of the plateau and extending to the crest of the Himalaya, the graben provides an opportunity to evaluate the kinematic relationships between east-west extensional strain in southern Tibet and north-south extensional strain in the Himalaya. Neotectonic and structural mapping of the Dangardzong fault along the western margin of the graben reveals a southward-decreasing component of normal slip coupled with a southward-increasing component of right-lateral slip that affects Pleistocene basin-fill sediments. We present 14C ages for river terraces in the Thakkhola graben that provide a ca. 17.2 ka minimum age on the latest stage of Dangardzong fault movement. Near the southern termination of the graben, the Dangardzong fault apparently offsets the Annapurna detachment, an early (Miocene) strand of the east-striking South Tibetan fault system. However, the Dangardzong fault itself terminates against a young (i.e., younger than ca. 17.2 ka) strand of the South Tibetan fault system, the Dhumpu detachment. Structural relationships among the Dangardzong, Annapurna, and Dhumpu faults suggest that the Dangardzong structure is a tear fault in the South Tibetan allochthon that accommodates differential amounts and rates of displacement along the South Tibetan fault system. Thus, although the South Tibetan fault system first developed as part of the structural architecture of the Himalaya in Miocene time, at least some strands have been active as recently as the Pleistocene. In a regional context, the South Tibetan fault system serves to accommodate the strain gradient between extension in Tibet and shortening in the Himalaya.