The Eskişehir Fault Zone is one of the major neotectonic structures of Turkey, extending from İnegöl (Bursa) to Cihanbeyli (Konya). The fault zone presents a considerable seismic risk for the city of Eskişehir but the exact locations of active segments and the source of the major seismic event, the 1956 earthquake (M = 6.5) that occurred in the instrumental period (from 1900 to 2013), have been debated in recent literature. The structural data obtained from field studies indicate an approximately N60W-trending main strand of the right lateral strike-slip Eskişehir Fault Zone. This trend corresponds to the en echelon bends on the course of the Sarısu River. Using this concurrence, the positions of Bahçehisar and the Çukurhisar-Sultandere segments are proposed and checked by seismic reflection studies. The seismic sections disclosing positive flower structures confirm the hypothesized position of the Çukurhisar-Sultandere segment. The relocation of epicenters and focal mechanism solutions of seismic events in 1956, 1990, 2010, and 2013 indicate that the Çukurhisar-Sultandere segment might be the rupture source of the 1956 event and is a possible potential seismic source for an earthquake that could seriously affect the Eskişehir settlement.