A high-resolution three-dimensional reconstruction of the 25-m.y.-old central Swiss Molasse Basin reveals two sedimentary domains separated by a ∼5-km-wide flood-plain. The proximal domain of the basin attained a width of 20 km, and its basement is steeply flexed (6°-7° dip). Petrographic data indicate that it was filled by sediment from the Rigi dispersal system derived from the central Alps of eastern Switzerland and by locally sourced bajadas. In contrast, the distal sedimentary domain, located farther north, was gently dipping (<2°) and was filled by the meandering Lac Léman and Honegg dispersal systems. Chronological data reveal that sedimentation in the northern proximal part of the basin started at ∼27 Ma, when sediment supply to the basin started to increase. Deflection of the foreland plate at ∼25 Ma is successfully simulated by flexural modeling of the thrust load and the sediment load. The model reveals that the Lac Léman and Honegg dispersal systems are located on a buried flexural bulge. Furthermore, it shows that burial and suppression of the flexural bulge at ∼27 Ma as well as an increase of the basin wavelength were controlled by the contemporaneous increase in the sediment supply rate of the Rigi system. The model presented suggests that the tectonic subsidence of the Molasse Basin was mainly controlled by tectonic events in the northern part of the orogen, within ∼70 km distance from the tip of the orogenic wedge. Crustal thickening in this part of the orogen is reflected in the proximal Molasse by sedimentary cycles characterized by an increase in the sediment accumulation rates up section and by the presence of locally sourced bajada fans at the top of each cycle. Although south vergent back thrusting along the Insubric Line ∼150 km south of the foreland basin contributed little to flexure, it resulted in an increase of the sediment supply to the foreland basin. This is reflected in the Molasse by coarsening and thickening upward trends, an increase of the basin wavelength, basinward shifts of the depocenters of the dispersal systems, and uplift and erosion of the proximal basin border.