The Nanbei River–Boli Fault is one of the largest NW-trending faults in Northeast China. However, limited data on the style and timing of recent earthquake activity on this fault greatly restrict the accuracy of seismic risk assessment. Here, we provide evidence of late Pleistocene to Holocene activity of the eastern segment of this fault for the first time. Specifically, the eastern segment of the Nanbei River–Boli Fault has experienced multiple earthquakes since the late Quaternary. Trench excavations indicate a recent strong earthquake at 7.28–2.11 ka, with approximately 1 m of co-seismic vertical displacement and preliminary estimates of the minimum vertical slip rates of 0.07–0.12 mm/a. According to a comprehensive analysis, we estimate that the eastern segment of the Nanbei River–Boli Fault can generate strong earthquakes of magnitude 7.0. This research provides important information for seismic risk assessments and seismic zoning, which can help seismic hazard assessment and mitigate their effects in Northeast China.