The largest earthquake ever recorded on land, the Assam Mw8.6 earthquake, occurred in the Eastern Himalayan Syntaxis (EHS), which has caused great concern regarding seismic hazard in this region. The seismic potential of the major faults in the EHS was evaluated by comparing the accumulation and release of seismic moments. First, constrained by the latest long-term global positioning system (GPS) measurements, the slip rates and locking depths of major faults in the EHS were calculated using a three-dimensional (3D) elastic block model. Second, the seismic moment release of the major faults in the EHS from 1800 to 2022 was estimated using an earthquake catalog. The results show that the seismic moment deficit of the western and eastern Bhutan and Assam segments of the Main Himalayan Thrust (MHT) are 2.6 × 10 21, 2.0 × 10 21 and 7.5 × 10 20 N · m, which are equivalent to seismic moments of Mw 8.3, 8.2 and 7.9, respectively. The MHT remains a major source of future seismic hazards in the EHS. In addition, the Jiali Fault and Naga Thrust were capable of generating earthquakes of Mw 7.4. This study also shows that if the seismicity of the MHT follows the Gutenberg–Richter (GR) law, the recurrence period of the Assam earthquake is approximately 2100 year.