New ages and strain analysis of syntectonic calcite from the west-central part of the North Anatolian fault zone (NAFZ; northern Turkey) shed light on the debate over the origin and reactivation behavior of this major active fault system. Contrasting views suggest that the west-central part of the NAFZ was already active during the mid-Eocene, mid-Miocene, or early Pliocene. The deformation style is also controversial: early stages of activity are associated with strike-slip, thrust, or normal faulting. Strike-slip deformation of the NAFZ marks the onset of tectonic escape of the Anatolian block westwards and is therefore a key player in tectonic reconstructions. We sampled syntectonic calcite from polished fault surfaces with horizontal slickenlines at four key sites along a 190-km-long sector of the NAFZ. All sites still show active faulting during the Holocene. Combined U-Pb ages (laser ablation–multicollector–inductively coupled plasma–mass spectrometry) and strain analyses of mechanically twinned calcite indicate that the west-central part of the NAFZ was associated with an extensional normal fault system at 42 Ma and reactivated as a dextral strike-slip fault at least 11 m.y. ago. The results indicate that the NAFZ evolved through the reactivation of major preexisting fault structures rather than by a gradual east (13 Ma) to west (5 Ma) propagation. The onset of westward translation of the Anatolian block occurred at least 11 m.y. ago, possibly as a result of the Miocene collision between the Arabian plate and Anatolian block.