This work presents new apatite fission track LA–ICP–MS (Laser Ablation Inductively Coupled Plasma Mass Spectrometry) data from Mid–Late Paleozoic rocks, which form the substratum of the Swiss Jura mountains (the Tabular Jura and the Jura fold-and-thrust belt) and the northern margin of the Swiss Molasse Basin. Samples were collected from cores of deep boreholes drilled in North Switzerland in the 1980s, which reached the crystalline basement. Our thermochronological data show that the region experienced a multi-cycle history of heating and cooling that we ascribe to burial and exhumation, respectively. Sedimentation in the Swiss Jura Mountains occurred continuously from Early Triassic to Early Cretaceous, leading to the deposition of maximum 2 km of sediments. Subsequently, less than 1 km of Lower Cretaceous and Upper Jurassic sediments were slowly eroded during the Late Cretaceous, plausibly as a consequence of the northward migration of the forebulge of the neo-forming North Alpine Foreland Basin. Following this event, the whole region remained relatively stable throughout the Paleogene. Our data show that the Tabular Jura region resumed exhumation at low rates in early–middle Miocene times (≈20–15 Ma), whereas exhumation in the Jura fold-and-thrust belt probably re-started later, in the late Miocene (≈10–5 Ma). Erosional exhumation likely continues to the present day. Despite sampling limitations, our thermochronological data record discrete periods of slow cooling (rates of about 1°C/My), which might preclude models of elevated cooling (due to intense erosion) in the Jura Mountains during the Miocene. The denudation (≈1 km) of the Tabular Jura region and the Jura fold-and-thrust belt (≈500 m) has provided sediments to the Swiss Molasse Basin since at least 20 Ma. The southward migration of deformation in the Jura mountains suggests that the molasse basin started to uplift and exhume only after 5 Ma, as suggested also by previous authors. The data presented here show that the deformation of the whole region is occurring in an out-of-sequence trend, which is more likely associated with the reactivation of thrust faults beneath the foreland basin. This deformation trend suggests that tectonics is the most determinant factor controlling denudation and exhumation of the region, whereas the recently proposed “climate-induced exhumation” mechanism might play a secondary role.