The curved left-lateral strike-slip Xianshuihe-Xiaojiang Fault System (XXFS) in southwestern China extends at least 1400 km in the eastern margin of the Tibetan Plateau. Fieldworks confirm that the XXFS is one of the longest and most seismically active faults in China. The strain released by the slip motion on the XXFS is related to the convergence between the Indian and Eurasian plates. The entire fault system has experienced at least 35 earthquakes of M > 6 in the recent 300 years and almost all segments of the system have been the locus of major historical earthquakes. Since the XXFS region is heavily populated (over 50 million people), understanding the migration of the large earthquakes in space and time is of crucial importance for the seismic hazard assessment in this region. We analyze a sequence of 25 earthquakes (M ≥ 6.5) that occurred along the XXFS since 1713, and investigate their influence on the 2008 Mw7.9 Wenchuan earthquake occurred on the adjacent Longmenshan fault. In our analysis, the relevant parameters for the earth crust are constrained by seismic studies. The locations and geometries of the earthquake faults as well as the rupture distributions are taken from field observations and seismological studies. Results from the Coulomb failure stress modeling indicate significant interactions among the earthquakes. After the 1713 earthquake, 19 out of 24 earthquakes occurred in the positive stress zone of the preceding earthquakes. The other 5 earthquakes located in the area without significant stress changes induced by the preceding events. In particular, we can identify 4 visible earthquake gaps with increasing seismic hazard along the XXFS, consistent with the findings from the paleo-seismological studies. The seismic activity and tectonic motion on the XXFS reduced the Coulomb stress accumulation at the hypocenter of 2008 Mw7.9 Wenchuan earthquake, implying that the Wenchuan earthquake might not be triggered directly by the seismic activities on the XXFS. On the other hand, the Coulomb failure stress induced by the Wenchuan earthquake has increased in a region of 125-km-long segment of the XXFS, northwest of Kangding City.