The Doruneh Fault System is one of the major transcurrent faults in central Asia, extending ~900 km from western Afghanistan into West-Central Iran. The left-lateral Doruneh Fault System is also a key structure in the Arabia–Eurasia collisional zone, bounding the northern margin of the independent Central Iranian Microplate. The Doruneh Fault System exhibits a curved geometry, and is divided here into three segments: Eastern, Central and Western. We present the results of geological, structural and geomorphic studies into the nature of recent activity along the Doruneh Fault System segments. A surprising observation is that small, relatively young drainage systems often show recent systematic left-lateral displacement across the fault, whereas large rivers indicate a former more complex right-lateral history. Furthermore, the existence of right-lateral offsets of pre-Pliocene rocks and S-C fabrics confirm this earlier phase of right-lateral movement on the fault. We suggest that the early right-lateral kinematics resulted from an earlier NW–SE-directed regional shortening, associated with the anticlockwise rotation of the Central Iranian Microplate. The shortening is characterized by the NE–SW-striking en échelon folds within the fault slivers, the right-lateral Taknar imbricate fan and the superimposed folding exposed north of Kashmar. Thus, assuming an initiation age of Eocene (55.8 Ma) for the fault, we estimate a former right-lateral slip rate of about 5.2–5.5 mm yr−1, which accompanied the 35° anticlockwise rotation of the Central Iranian Microplate. According to our study, the youngest units exhibiting right-lateral displacement are Middle Miocene in age, suggesting a post-Middle Miocene timing for the onset of slip-sense inversion.