The Hindu Kush-Pamir region of southern Asia is one of Earth's most rapidly deforming regions and it is poorly understood. This study develops a kinematic model based on active faulting in this part of the Trans-Himalayan orogenic belt. Previous studies have described north-verging thrust faults and some strike-slip faults, reflected in the northward-convex geomorphologic and structural grain of the Pamir Mountains. However, this structural analysis suggests that contemporary tectonics are changing the style of deformation from north-verging thrusts formed during the initial contraction of the Himalayan orogeny to south-verging thrusts and a series of northwest-trending, dextral strike-slip faults in the modern transpressional regime. These northwest-trending fault zones are linked to the major right-lateral Karakoram fault, located to the east, as synthetic, conjugate shears that form a right-stepping en echelon pattern. Northwest-trending lineaments with dextral displacements extend continuously westward across the Hindu Kush-Pamir region indicating a pattern of systematic shearing of multiple blocks to the northwest as the deformation effects from Indian plate collision expands to the north-northwest. Locally, east-northeast- and northwest-trending faults display sinistral and dextral displacement, respectively, yielding conjugate shear pairs developed in a northwest-southeast compressional stress field. Geodetic measurements and focal mechanisms from historical seismicity support these surficial, tectono-morphic observations. The conjugate shear pairs may be structurally linked subsidiary faults and co-seismically slip during single large magnitude (> M7) earthquakes that occur on major south-verging thrust faults. This kinematic model provides a potential context for prehistoric, historic, and future patterns of faulting and earthquakes.