In this study, apatite fission track (AFT) analyses from opposite sides of the Jianglisai fault are used to constrain the timing of fault activity. Samples collected on the hanging wall have AFT ages between 10 ± 1 and 15 ± 2 Ma and a mean track length ranging from 13.1 ± 0.2 to 13.5 ± 0.2 μm. Samples collected on the footwall have AFT ages between 7.4 ± 0.6 and 9.0 ± 0.9 Ma and a relatively short mean track length that ranges from 11.3 ± 0.2 to 11.6 ± 0.2 μm. AFT modeling revealed that each side experienced two rapid cooling events that were related to tectonic stresses and deformation propagating in a northwestern direction. Combined with electron spin resonance dating constraints, we interpret the rapid cooling of the hanging wall during the Middle Miocene (17–14 Ma) as having recorded that the Jianglisai fault has been active at or prior to ~17 Ma. Both sides of the fault recorded the exhumation event that occurred at approximately 8 Ma, which is responsible for developing the fold-and-thrust belt along the mountain front. The Early Pliocene (about 5 Ma) cooling event indicated that the thrusting-related exhumation in the Jianglisai fault system was a continuously gradual intensified process. The North Altyn Tagh fault system was formed through stepwise thrusting from southeast to northwest during the Middle Miocene to Early Pliocene (17–5 Ma). Since then, the rigid Tarim plate provided constraint on the northward propagation, which likely caused the change from compressional thrusting to thrusting with a left-lateral strike-slip component of the North Altyn Tagh fault system.