In West Anatolia near the cities of Izmir and Manisa, the historical occurrence of large earthquakes suggests the presence of important seismogenic faults. However, these faults have yet to be investigated in detail. The Manisa Fault Zone (MFZ) is an active large-scale normal fault system in this area, and thus field observations and palaeoseismological studies of this zone are important for predicting future earthquakes. Hence we sought to document geological and palaeoseismological evidence for Holocene activity on the MFZ. We performed trenching to determine the magnitude and timing of past surface-faulting events using detailed fault-trace mapping, measurements of Upper Pleistocene-Lower Holocene sediments, and radiocarbon dating. By comparing the trench data with palaeoearthquake records, we find evidence for three palaeoearthquakes which correspond to 926 AD, 1595 or 1664 AD, with the most recent event in 1845 AD. We also find this in the central and western sectors of the MFZ, which together with the eastern sector comprise the three major seismogenic zones. The Pliocene-Quaternary vertical off set at fault scarps is far less than that in the western sector, suggesting that activities of these sectors are highly independent. Evaluation of field observations suggests that the MFZ has been the source of multiple Late Pleistocene and Holocene surface-rupturing earthquakes. Our results constitute the first palaeoseismic evidence on the causative faults of historical earthquakes that affected Manisa, and point to their underlying tectonic mechanisms.