In this paper we investigate the tectonics of the central Swiss Molasse Basin (SMB), situated between the central European Alps and the Jura fold‐and‐thrust belt. Based on (re)interpreted 2‐D reflection seismic data and geological 3‐D modeling, we present new insights into the structural configuration and evolution of the central SMB. During the thin‐skinned, main deformation phase of the Jura fold‐and‐thrust belt (~12–4 Ma), the central SMB was riding passively above a major detachment horizon within Triassic evaporites, which roots beneath the External Crystalline Massifs of the Central Alps. In the SMB, low‐amplitude detachment folds and detachment‐rooted WSW‐ENE striking thrust and reverse faults are related to this event. Younger, major NNE‐SSW and NNW‐SSE trending strike‐slip fault zones cross the basin over a length of several kilometers, affecting the Cenozoic and Mesozoic cover units and extending into the pre‐Mesozoic crystalline basement. In cases, the fault zones apparently reactivate inherited, Permo‐Carboniferous trough (PCT) bounding, Paleozoic normal faults. Seismic data further reveal mild inversion of WSW‐ENE striking PCTs. These structures clearly cut the basement‐cover contact, thus postdating the main deformation phase of the Jura fold‐and‐thrust belt. Present‐day earthquake focal mechanisms and epicenter distribution show strike‐slip faulting and basement‐seated seismicity, respectively, thus corroborating our observations from seismic interpretation. Our data suggest a change from late Miocene thin‐skinned to Pliocene to present‐day incipient thick‐skinned tectonics. This major change reflects the establishment of a midcrustal detachment and may be related to changes in slab dynamics of the subducting European lithosphere.