The Afghan-Tajik Basin in southern Tajikistan is poised to become a major gas province in Central Asia and contains a record of early orogenesis for the Pamir Mountains, the western Tibetan Plateau, and the Tien Shan. As a result, the Tajik Basin is of significant economic importance and provides an opportunity to study early basin formation in the Trans-Himalayan orogenic system. However, the area has remained almost unexamined since the collapse of the Soviet Union and the evolution of the basin, including its burial history and origin remain unclear. This study aims to unravel the origin of the Tajik Basin and reconstruct the Mesozoic to Paleogene depositional systems, immediately prior to widespread unroofing and exhumation of the Pamir in the Neogene. This will be achieved through subsidence and basin history analyses using depositional facies models based on measured sections, well log data, and assorted analytical methods including vitrinite reflectance, detrital zircon dating, and apatite fission track modeling. Russian geologists from the middle of last century suggested that the Tajik Basin originated as a back-arc or intracratonic basin in the Mesozoic, however, a careful review of measured stratigraphic sections reveals significant clastic input throughout the Cretaceous and regionally extensive unconformities and anomalous water depth variations in the early Paleogene. In addition, regional geologic syntheses indicate that the southern Eurasian margin was a Cordilleran-style subduction margin in the Cretaceous, which hints that the Tajik Basin may have existed as a retroarc foreland basin.